# ent

id: cord-002608-zn7tm1ww
type: DNA
entity:
  primer pairs SINV nt9300F 5 GCACCGCCATCAAGCAATGTGTGGC 3 SINV nt9300R 5 CAATTTC CCTTGGGCCGTGTGGTCG 3 SINV nt10100F 5 TGTTCCAAATGTGCCACAGATACCG 3 SINV nt10100R 5 AATGT ACTCTTGGTTGGTGGAAGGC 3 SINV nt10400F 5 CAGCAGATTGCGCGTCTGACCATGC 3 SINV nt10400R 5 GACTCC GTTCACGTACACATCTAGG 3


id: cord-002608-zn7tm1ww
type: CHEMICAL
entity:
  amino terminal peptides of alfalfa mosaic virus coat protein The EMBO journal Coat protein binding sites on RNA 1 of alfalfa mosaic virus Removal of the N terminal part of alfalfa mosaic virus coat protein


id: cord-006129-5rog0s98
type: GGP
entity:
  Hodgkin s lymphoma T cell lymphoma nasopharyngeal carcinoma and gastric tumor 61 During the active phase of EBV infection more than 100 genes


id: cord-004501-guiy89x8
type: WORK_OF_ART
entity:
  Viral Skin Diseases Viral Gastroenteritis in the Adult Population Viral Gastroenteritis in Adults Epidemiology of gastroenteritis


id: cord-004501-guiy89x8
type: ORG
entity:
  the Management of HIV Infection A Review of the Toxicity of HIV Medications Efficacy of Tenofovir 1 Vaginal Gel


id: cord-004501-guiy89x8
type: ORG
entity:
  Pharmacodynamics Modeling and Simulation Systems to Support the Development and Regulation of Liposomal Drugs


id: cord-006450-si5168pb
type: TAXON
entity:
  viruses herpes simplex virus HSV 1 n 27 cytomegalovirus CMV n 23 Epstein Barr virus EBV n 18 human herpesvirus HHV 6 n 12 respiratory syncytial virus RSV n 3 rhinovirus n 1


id: cord-003045-r707jl16
type: PROTEIN
entity:
  ChLIA Indirect fluorescent antibody IFA Western blot WB Polymerase Chain Reaction PCR and Rapid immunoassays 1


id: cord-000346-9b6yz3f4
type: DISEASE
entity:
  critically reduce viral fitness 11 With a location on the framework residue of the enzyme catalytic site 12 the mutation


id: cord-016798-tv2ntug6
type: TAXON
entity:
  syncytial virus bovine adenovirus bovine rhinovirus bovine coronavirus bovine reovirus bovine enterovirus


id: cord-016475-7ldxvbpz
type: CHEMICAL
entity:
  interferon alpha beta system in antiviral responses a multimodal machinery of gene regulation by the IRF


id: cord-011095-79ce5900
type: PROTEIN
entity:
  intracellular adhesion molecule 1 ICAM 1 P5 homologous fimbriae P5 fimbriae carcinoembryonic adhesion molecule 1 CEACAM 1


id: cord-016499-5iqpl23p
type: PROTEIN
entity:
  cytokine protein NK natural killer PBMC peripheral blood mononuclear cells IL interleukin TNF tissue necrosis factor TSLP


id: cord-016499-5iqpl23p
type: DISEASE
entity:
  human rhinoviruses paramyxoviruses coronaviruses and bocavirus during acute respiratory tract infections


id: cord-018325-k69h9cc5
type: DISEASE
entity:
  coronaviruses adenoviruses respiratory syncytial virus RSV influenza viruses and parainfluenza viruses


id: cord-009101-376snefs
type: DNA
entity:
  neonatal intensive care unit Human parvovirus Bl9 The biology of viruses Vertical transmission of hepatitis A


id: cord-018430-u3k8pds6
type: DISEASE
entity:
  sinoatrial block atrial standstill AV block intraatrial conduction abnormalities atrial tachycardia flutter


id: cord-020235-stcrozdw
type: DNA
entity:
  OGHM 1 Augenklinik d justus Liebig Univ 0 6300 Giessen 2 Inst f Neuropathologie u Virologie Freie Univ 0 1000 Berlin Retino Cerebral Manifestation


id: cord-020235-stcrozdw
type: WORK_OF_ART
entity:
  Mikrobiologie Abr Virologie d TU Biedersteiner Str 29 Antibodies against Influenza C Virus in the Population of Germany Kenia


id: cord-022349-z8w1wkm8
type: WORK_OF_ART
entity:
  Freeze drying Temperature Stable Vaccines for Developing Countries Significance and Development Strategies


id: cord-023143-fcno330z
type: GGP
entity:
  e i t h e r U S 1 1 o r US2 6 gene products s i g n i f i c a n t l y reduced l e v e l s of MHC class I heavy chain


id: cord-023143-fcno330z
type: ORG
entity:
  CNS encephalomyelitis Division of Retrovirology Walter Reed Army Institute of Research and Henry M Jackson Foundation


id: cord-023143-fcno330z
type: DISEASE
entity:
  T cell recognition Investigations of the characteristics of the enzymes contributing to the degradation of the Gpt have shown that a reducing environment is essential as diamide treatment


id: cord-262585-5vjqrnwh
type: DISEASE
entity:
  herpes simplex virus 2 Herpes simplex virus 2 ICP34 5 confers neurovirulence by regulating the type I interferon response An N terminal arginine


id: cord-262776-6k7tcgfs
type: ORG
entity:
  Animal Health Report of the Federation of European Laboratory Animal Science Associations FELASA Working Group


id: cord-262753-jld1ygxt
type: PROTEIN
entity:
  primary antibodies rabbit anti eIF3a Cell Signaling 3411 rabbit anti eIF4E Cell Signaling 9742 rabbit anti 4E BP1 Cell Signaling 9452 rabbit anti phospho 4E BP1 Ser65 Cell Signaling 9451 rabbit anti phospho 4E BP1 Thr37 46 Cell Signaling 2855 mouse anti actin Millipore MAB1501 mouse anti actin


id: cord-262753-jld1ygxt
type: DISEASE
entity:
  influenza A virus a segmented negative strand RNA virus that replicates in the nucleus 50 of the total mRNA in the cytoplasm is viral 48 In this case however the viral endonuclease PA X degrades cellular mRNA which further contributes to the dominance of viral mRNA 66 67 For vaccinia virus a DNA virus that replicates entirely within the cytoplasm degradation


id: cord-259233-smmhhroe
type: DISEASE
entity:
  HIV 1 viral budding 106 107 108 Nevertheless interferon stimulated gene 15 protein ISG 15 inhibits HIV 1 egression


id: cord-272655-qeojdpez
type: ORG
entity:
  the Epidemiological Surveillance System Sistema de Vigilancia Epidemiológica Nacional Sivigila Samples


id: cord-274749-ji91qq9q
type: DISEASE
entity:
  respiratory syncytial virus RSV influenza virus INF types A and B adenovirus AV parainfluenza virus PIV human metapneumovirus HMPV and rhinovirus RV 3 4 5


id: cord-274080-884x48on
type: DNA
entity:
  e g SV40 polyomavirus mouse or macropinocytosis e g vaccinia virus respiratory syncytial virus Ebola virus HIV 1 Blaas 2016 Cossart and Helenius 2014 Fields and Knipe 2013 Kirkham and Parton 2005 Marechal


id: cord-274080-884x48on
type: LAW
entity:
  the paramyxovirus fusion glycoprotein superiority of furin PACE to PC2 or PC1 PC3 Development of novel


id: cord-274080-884x48on
type: DISEASE
entity:
  human immunodeficiency virus Type 1 protease activity Viral and host proteins that modulate filovirus budding Rapid and automated fluorescencelinked immunosorbent assay


id: cord-281916-v6u5mr2i
type: DNA
entity:
  ERV3 human endogenous retrovirus 3 Flu influenzae virus HBoV human bocavirus HCoV human coronavirus hMPV human metapneumovirus PCR polymerase chain reaction PIV paraInfluenza virus RhV EV rhino entero virus RNA ribonucleic acid ROC receiver


id: cord-276908-9jthjf24
type: PROTEIN
entity:
  autophagosome Potential transmembrane scaffold protein double membrane vesicle DMV formation 20 nsp7


id: cord-276908-9jthjf24
type: CHEMICAL
entity:
  oregano oil fennel garlic peppermint echinacea sambucus licorice astragalus ginger tulsi ocimum tenuiflorum turmeric


id: cord-276908-9jthjf24
type: CHEMICAL
entity:
  coriandrin apple peels ursolic acid cucurbit vegetables hederagenin olive oil oleanolic acid rosemary mint


id: cord-270294-g95skuik
type: DISEASE
entity:
  influenza human metapneumovirus hMPV respiratory syncytial virus RSV rhinovirus parainfluenza virus 1 4 coronaviruses OC43 229E and NL63 and adenovirus Results A total of 193


id: cord-286337-qk90xb3a
type: CELL_TYPE
entity:
  gut helper T cell responses Respiratory influenza virus infection induces intestinal immune injury via microbiota mediated Th17 cell


id: cord-286337-qk90xb3a
type: GGP
entity:
  i e Streptococcus Prevotella Veillonella Streptococcus Haemophilus Neisseria Streptococcus Moraxella Haemophilus


id: cord-266147-s8rxzm0t
type: LAW
entity:
  1 Contribution and Interpretation of Studies Validating the Inactivation and Removal of Viruses revised Inactivation


id: cord-286219-qcx5ehnh
type: PROTEIN
entity:
  cullin4A DDB1 DCAF1 Ub ligase complex 130 156 157 158 159 160 161 162 a binding that is required for the induction of the G2 arrest 163


id: cord-286219-qcx5ehnh
type: DISEASE
entity:
  herpes simplex virus type 1 gB and virus egress require functional biogenesis of multivesicular bodies Human cytomegalovirus exploits


id: cord-280048-b4dz1lnn
type: WORK_OF_ART
entity:
  Thinking Outside the Triangle Replication Fidelity of the Largest RNA Viruses Theoretical Models of Generalized Quasispecies Alterations


id: cord-280048-b4dz1lnn
type: ORG
entity:
  Differential Shape of Geminivirus Mutant Spectra Across Cultivated and Wild Hosts With Invariant Viral Consensus Sequences Genetic


id: cord-289093-si8btsab
type: DNA
entity:
  HIV 1 41 42 43 West Nile Virus WNV 44 Hepatitis C Virus HCV 30 45 Vesicular Stomatitis Virus VSV 29 Borna Disease Virus 46 enteroviruses 27 Dengue virus 28 herpes simplex virus 1 HSV 1 33


id: cord-287459-k9x3z2h1
type: ORG
entity:
  the Chinese Center for Disease Control and Prevention Detection of Covid 19 in Children in Early Rhinovirus


id: cord-292416-3hhi4wps
type: DISEASE
entity:
  HIV and HCV which even after many years of research and huge development budget are yet to have an effective and safe vaccine Furthermore even once a safe and effective vaccine is devel oped billions of doses have to be manufactured and distributed worldwide The urgent need to control the spread of the SARS CoV 2 outbreak


id: cord-286137-4cbh3u3z
type: WORK_OF_ART
entity:
  Prolonged Influenza Virus Shedding and Emergence of Antiviral Resistance in Immunocompromised Patients and Ferrets Oseltamivir


id: cord-287758-da11ypiy
type: PROTEIN
entity:
  amino acids Proline Leucine Lysine Asparagine Phenylalanine Glycine Threonine Glutamine Alanine Methionine and Tyrosine One


id: cord-287758-da11ypiy
type: CHEBI
entity:
  amino acids Proline Leucine Lysine Asparagine Phenylalanine Glycine Threonine Glutamine Alanine Methionine


id: cord-287758-da11ypiy
type: ORG
entity:
  the Humoral Immune Response Contributes to Virus Spread and Immunopathology in the Airways of Murine Models


id: cord-287758-da11ypiy
type: WORK_OF_ART
entity:
  A Possible Pharmaceutical Treatment for COVID 19 Experimental Treatment with Favipiravir for COVID 19


id: cord-287758-da11ypiy
type: ORG
entity:
  Association of Treatment with Hydroxychloroquine or Azithromycin With In Hospital Mortality in Patients With COVID 19


id: cord-287758-da11ypiy
type: DISEASE
entity:
  cardiovascular issues cerebrovascular chronic pulmonary diseases immunocompromising renal problems hepatic disease hypertension diabetes


id: cord-294478-3ickafd3
type: ORG
entity:
  United States Department of Health and Human Services Centers for Disease Control and Prevention Animals


id: cord-298033-kzdp9edn
type: CHEMICAL
entity:
  Relenza 2R 3R 4S 4 guanidino 3 prop 1 en 2 ylamino 2 1R 2R 1 2 3 trihydroxypropyl 3 4 dihydro 2H pyran 6 carboxylic acid 8 4 Resistance


id: cord-298033-kzdp9edn
type: CHEMICAL
entity:
  Zalcitabine ddC 4 amino 1 2R 5S 5 hydroxymethyl tetrahydrofuran 2 yl pyrimidin 2 1H one 12 2R 3R 4R 5R 5 2 4 dioxopyrimidin 1 yl 4 fluoro 3 hydroxy 4methyl tetrahydrofuran 2 yl methoxy phenoxy phosphoryl amino propanoate


id: cord-294592-zwvr57a0
type: WORK_OF_ART
entity:
  RNA Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus Host Interactions


id: cord-303330-zh8wzza5
type: ORG
entity:
  Impact of SARS CoV 2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients with Coronavirus Disease


id: cord-303330-zh8wzza5
type: DISEASE
entity:
  coronary artery disease congestive heart failure cerebrovascular disease hypertension chronic obstructive pulmonary disease COPD chronic kidney disease


id: cord-307354-dkwcheu0
type: DISEASE
entity:
  herpes simplex virus 1 vhs protein enhances translation of viral true late mRNAs and virus production


id: cord-297960-4x1j0iqg
type: PROTEIN
entity:
  CD44 antigen CD44 Serine arginine repetitive matrix protein 2 SRRM2 Myristoylated alaninerich C kinase substrate MARCKS BAG family molecular chaperone regulator 3 BAG3


id: cord-317037-1qydcc5e
type: CELL_LINE
entity:
  HepAD38 Cell Line Hepatitis B Virus Encoded MicroRNA Controls Viral Replication HTLV 1 Extracellular Vesicles Promote Cell to


id: cord-317037-1qydcc5e
type: GGP
entity:
  proteins spike glycoprotein S nucleocapsid protein N membrane protein M small envelope glycoprotein E several nonstructural proteins


id: cord-317037-1qydcc5e
type: WORK_OF_ART
entity:
  Human Papilloma Virus Infected Cervical Cancer Cells Enhance HIV 1 Replication in Differentiated U1 Cell Line Circulatory Astrocyte


id: cord-317037-1qydcc5e
type: WORK_OF_ART
entity:
  Potential Biomarkers of Neurological Dysfunction in HIV Infected Subjects and Alcohol Tobacco Users Dependence


id: cord-317037-1qydcc5e
type: WORK_OF_ART
entity:
  Proteomic Analysis of Exosomes Derived from Inducible Hepatitis B Virus Replicating HepAD38 Cell Line Hepatitis B Virus


id: cord-317037-1qydcc5e
type: WORK_OF_ART
entity:
  Macrophage Derived Extracellular Vesicles Induce Long Lasting Immunity Against Hepatitis C Virus Which Is Blunted by Coronavirus


id: cord-318495-1w74wf02
type: ORG
entity:
  Low Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles


id: cord-318495-1w74wf02
type: ORG
entity:
  Sarcoma Associated Herpesvirus Activate Lytic Replication by Triggering Differentiation Signaling Ultrastructural


id: cord-317277-rr9zue4l
type: DISEASE
entity:
  human immunodeficiency virus type 1 cell to cell spread at the virological synapse African swine fever


id: cord-317277-rr9zue4l
type: DISEASE
entity:
  human immunodeficiency virus type 1 and simian immunodeficiency virus Glycoproteins gE and gI are required


id: cord-317277-rr9zue4l
type: DISEASE
entity:
  herpes simplex virus and pseudorabies virus entry The postbinding activity of scavenger receptor class B type I


id: cord-302111-kg0dmgq0
type: PROTEIN
entity:
  influenza M2 protein M2e or hemagglutinin stalk domains Hemagglutinin globular head specific antibodies


id: cord-302111-kg0dmgq0
type: WORK_OF_ART
entity:
  The Clinical Presentation and Immunology of Viral Pneumonia and Implications for Management of Coronavirus Disease


id: cord-318853-mxyxwkhx
type: PROTEIN
entity:
  lipoprotein LDL receptors 85 86 transferrin receptor TfR 87 asialoglycoprotein receptor ASGP R 88 89


id: cord-318853-mxyxwkhx
type: GGP
entity:
  acetylcholine receptors 76 serotonergic neurotransmitters 5HT 77 endothelial cell glycoproteins 78 insulin


id: cord-319761-bu5pzbnv
type: PROTEIN
entity:
  paramyxoviruses simian virus 5 and human parainfluenza virus type 2 Latency associated nuclear antigen


id: cord-319761-bu5pzbnv
type: DISEASE
entity:
  adenovirus Epstein barr virus EBV BHRF1 protein and other viruses 17 18 There are several classes of caspase inhibitors


id: cord-304424-048xo7jn
type: CELL_LINE
entity:
  Merkel cell polyomavirus human bocavirus 2 salivirus Lujo arenavirus Dandenong arenavirus SFTS bunyavirus


id: cord-304424-048xo7jn
type: DISEASE
entity:
  influenza A H1N1 pdm09 virus Full length transcriptome assembly from RNA Seq data without a reference genome ssRNA viruses from biotrophic Oomycetes


id: cord-325230-3kg4oe4g
type: CHEMICAL
entity:
  amino terminal amino acid of 2A pro and the carboxy terminal residue of the capsid protein VP1 Aphthovirus L


id: cord-325230-3kg4oe4g
type: CHEMICAL
entity:
  amino terminal residue of aphthovirus 2B 15 16 To achieve this a short peptide harbouring an NPG P motif the parentheses mark the interruption site is sufficient Short 2A peptides from erboviruses 17 teschoviruses 18 senecaviruses 19 and cosaviruses 20


id: cord-320015-lbr2q4qh
type: PROTEIN
entity:
  ribonucleotide reductase 79 80 thymidine kinase 30 thymidylate synthase dUTPase 81 purine nucleoside phosphorylase PNP


id: cord-326273-6rp12py3
type: CELL_LINE
entity:
  CD68 histiocyte population Table 3 SARS severe acute respiratory syndrome positive strong positive negative intermediate Antisense oligonucleotide probes


id: cord-326273-6rp12py3
type: ORG
entity:
  Detection of Severe Acute Respiratory Syndrome Associated Coronavirus in Pneumocytes of the Lung date 2004


id: cord-325750-x7jpsnxg
type: DNA
entity:
  human immunodeficiency virus 36 simian retroviruses 37 38 39 40 and hepatitis E virus 41 However PCR


id: cord-331673-xv1tcugl
type: ORG
entity:
  Novel Emerging Antiviral Therapeutic Agents High Efficiency of Functional Carbon Nanodots as Entry Inhibitors


id: cord-331673-xv1tcugl
type: ORG
entity:
  Feline Calicivirus Novel Antiviral Characteristics of Nanosized Copper i Iodide Particles Showing Inactivation Activity


id: cord-331673-xv1tcugl
type: WORK_OF_ART
entity:
  Replication by Affecting Virus Maturation without Impairing Protease Activity A New Family of Fullerene Derivatives


id: cord-331673-xv1tcugl
type: WORK_OF_ART
entity:
  Versatile Nanoplatform for Entrapment of Guanine Based Drugs Intracellular Trafficking and Therapeutic Outcome of Multiwalled Carbon Nanotubes


id: cord-331673-xv1tcugl
type: WORK_OF_ART
entity:
  Nanoparticles Promoting Both Humoral and Cellular Immune Responses to HCV Recombinant Proteins DNA Vaccines


id: cord-331673-xv1tcugl
type: ORG
entity:
  Immunization Nanodiamond Enhances Immune Responses in Mice against Recombinant HA H7N9 Assessment of Gold Nanoparticles


id: cord-331673-xv1tcugl
type: ORG
entity:
  a Size Dependent Vaccine Carrier for Enhancing the Antibody Response against Synthetic Foot And Mouth Disease Virus Peptide Consensus M2e Peptide Conjugated to Gold Nanoparticles Confers Protection


id: cord-331673-xv1tcugl
type: DISEASE
entity:
  Herpes Simplex Virus Type 1 Interaction of Silver Nanoparticles with HIV 1 Silver Nanoparticles Impair Peste Des Petits


id: cord-320713-b37c8aye
type: SO
entity:
  initiation factor eIF4G with type 1 internal ribosomal entry sites Polypyrimidine tract binding protein


id: cord-320713-b37c8aye
type: GGP
entity:
  MAP kinase pathways Internal ribosome entry site within hepatitis C virus RNA Adenovirus VA1 noncoding RNA


id: cord-320713-b37c8aye
type: DISEASE
entity:
  human immunodeficiency virus transactivator protein The integrity of the stem structure of human immunodeficiency virus type 1


id: cord-328259-3g4klpyg
type: ORG
entity:
  DIAMOND MEGAN Community Edition Interactive Exploration and Analysis of Large Scale Microbiome Sequencing Data Linking


id: cord-328259-3g4klpyg
type: ORG
entity:
  Active Crossfire Between Cyanobacteria and Cyanophages in Phototrophic Mat Communities Within Hot Springs Fast


id: cord-306921-3afgpunj
type: PROTEIN
entity:
  N ethylmaleimide sensitive factor attachment receptor SNARE protein syntaxin 17 STX17 synaptosome associated protein 29 SNAP29


id: cord-306921-3afgpunj
type: GGP
entity:
  coxsackievirus A16 a case report Acute kidney injury secondary to severe hand foot and mouth disease caused by Enterovirus A71


id: cord-330200-l6bnxi40
type: DISEASE
entity:
  abnormal white blood cell count 9 27 3 neutrophil All rights reserved No reuse allowed without permission which


id: cord-346290-my8ow5ee
type: ORG
entity:
  the International Committee on Taxonomy of Viruses International Union of Microbiological Societies Transmission


id: cord-346290-my8ow5ee
type: ORG
entity:
  the European Society of Clinical Microbiology and Infectious Diseases ESCMID Study Group on Respiratory Viruses ESGREV


id: cord-339288-y8woqsii
type: WORK_OF_ART
entity:
  RNA replicon Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line Packaged replicons of bovine viral diarrhea virus


id: cord-338083-77re4l0w
type: DISEASE
entity:
  Mannheimia haemolytica bovine herpesvirus 1 and bovine respiratory syncytial virus Bovine viral diarrhea virus infections


id: cord-329306-p5wmqmvj
type: DISEASE
entity:
  influenza A H5N1 virus and the 2009 pandemic influenza A H1N1 virus raised the importance of lower respiratory tract viral infections


id: cord-332632-u2ud0vmq
type: ORG
entity:
  Institute of Virology and Immunology of the Vetsuisse Faculty University of Bern the Federal Food Safety and Veterinary Office


id: cord-343470-w215pzdc
type: CHEMICAL
entity:
  N 6 methyladenosine m 6 A 5 methylcytidine m 5 C N 4 acetylcytidine ac 4 C and 2 O methylation of the ribose moiety of


id: cord-342133-khrljehj
type: DNA
entity:
  NP 1 target 0 125 μL of probe 5 CCAGGATTGGGTGGAACCTGCAAA 3 or 5 AGGCTCGGGCTCATATCATCAGGAACA 3 and 2 5 μL of sample viral DNA PCRs


id: cord-342133-khrljehj
type: DNA
entity:
  reverse primers 5 CACAGACAGAAGCAGACGAGAT 3 and 5 GGTG AGAAGTGACAGCTGTATTG 3 5 TTCAGAATGGTCACCTCTACA 3 and 5 CTGTGC TTCCGTTTTGTCTTA 3 5 AACTTTGACTGTGAATGGGTTA 3 and 5 AAATAGTGCC TGGAGGATGAT 3 5 CTATCACCAGAGAAAATCCAATC 3 and 5 GAGACGGTAACA CCACTA 3


id: cord-345168-3w32v2fm
type: DISEASE
entity:
  influenza A H1N1 virus after vaccination with seasonal influenza vaccine Comparison of nasopharyngeal flocked swabs


id: cord-353554-98uzivsk
type: DISEASE
entity:
  Dilated 218 cardiomyopathy Hypertrophic cardiomyopathy Arrhythmogenic right 219 ventricular cardiomyopathy


id: cord-346916-jj4l9ydl
type: GGP
entity:
  p38 mitogen activated protein kinase MAPK c Jun N terminal kinase JNK signal transducer and activator of transcription 1 and 3 STAT1


id: cord-355872-z6vsjmxn
type: DISEASE
entity:
  influenza and respiratory syncytial viruses Evaluation of the BioFire FilmArray respiratory panel and the GenMark eSensor respiratory viral panel


# bib

id: cord-000346-9b6yz3f4
author: Holder, Benjamin P.
date: 2011-03-24
txt: ./txt/cord-000346-9b6yz3f4.txt
cache: ./cache/cord-000346-9b6yz3f4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063785/
doi: 10.1371/journal.pone.0014767
summary:
  In order to obtain two complementary views of the infection kinetics for the A/Brisbane/59/2007 WT and H275Y mutant strains, virus growth over time was observed in two different in vitro systems: the viral plaque assay and the multiple-cycle viral yield assay. We are left then with two experimental measures -the viral titer growth rate and the plaque velocity -whose values may depend on three unknown infection kinetics parameters: the infecting time, t inf ; the latent infection period, t L ; and the infectious lifespan of a cell, t I . To demonstrate this concept using the A/ Brisbane/59/2007 (H1N1) WT and H275Y mutant strains, we have plotted the experimentally-measured values of plaque velocity and viral titer growth rate as functions of the infecting time and latent infection period, using the model dependence determined above ( Figure 6 ).

title:
  Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model

abstract:
  In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008–2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1–3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness.


id: cord-001340-kqcx7lrq
title: Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing
author: Ladner, Jason T.
date: 2014-06-17
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068259/
doi: 10.1128/mbio.01360-14
abstract:
  Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five “standard” categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques.


id: cord-001985-iwfidoer
title: FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance
author: Urayama, Syun-ichi
date: 2016-02-13
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791113/
doi: 10.1264/jsme2.me15171
abstract:
  Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.


id: cord-002608-zn7tm1ww
author: Sokoloski, Kevin J.
date: 2017-06-29
txt: ./txt/cord-002608-zn7tm1ww.txt
cache: ./cache/cord-002608-zn7tm1ww.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507600/
doi: 10.1371/journal.ppat.1006473
summary:
  A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. This report details our efforts to identify and characterize the sites of interaction between the viral capsid protein and the genomic RNA using the model alphavirus Sindbis virus (SINV). C) The infectivity of the individual SINV C:R interaction site mutants and parental wild type virus as reported as the ratio of total particles per infectious unit as determined using BHK-21 cells.

title:
  Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants

abstract:
  Alphaviruses are arthropod-borne viruses that represent a significant threat to public health at a global level. While the formation of alphaviral nucleocapsid cores, consisting of cargo nucleic acid and the viral capsid protein, is an essential molecular process of infection, the precise interactions between the two partners are ill-defined. A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. Mutational analyses of the cytoplasmic viral RNA-capsid interaction sites revealed a functional role for capsid binding early in infection. Interaction site mutants exhibited decreased viral growth kinetics; however, this defect was not a function of decreased particle production. Rather mutation of the cytoplasmic capsid-RNA interaction sites negatively affected the functional capacity of the incoming viral genomic RNAs leading to decreased infectivity. Furthermore, cytoplasmic capsid interaction site mutants are attenuated in a murine model of neurotropic alphavirus infection. Collectively, the findings of this study indicate that the identified cytoplasmic interactions of the viral capsid protein and genomic RNA, while not essential for particle formation, are necessary for genomic RNA function early during infection. This previously unappreciated role of capsid protein during the alphaviral replication cycle also constitutes a novel virulence determinant.


id: cord-003045-r707jl16
title: viGEN: An Open Source Pipeline for the Detection and Quantification of Viral RNA in Human Tumors
author: Bhuvaneshwar, Krithika
date: 2018-06-05
txt: ./txt/cord-003045-r707jl16.txt
cache: ./cache/cord-003045-r707jl16.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996193/
doi: 10.3389/fmicb.2018.01172
summary:
  The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups. Available online at: https:// www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/ licensedproductsblas/blooddonorscreening/infectiousdisease/ucm080466.htm Abbreviations: HBV, Hepatitis B virus; HCV, Hepatitis C Virus; HERV K113, Human Endogenous Retrovirus K113; TCGA, The Cancer Genome Atlas; HCC, Hepatocellular carcinoma; NAFLD, nonalcoholic fatty liver disease; Hep B, Hepatitis B; Hep C, Hepatitis C; HepB + HepC, coinfected with both Hepatitis B and C virus; HBsAg, Hepatitis B surface antigen; HBeAg, Hepatitis B type e antigen; NGS, next-generation sequencing; RNA-seq, whole transcriptome sequencing; BAM, Binary version of Sequence alignment/map format; CDS, coding sequence; Cox PH, Cox Proportional Hazard; HBx, viral gene X; STS, Sequence-tagged sites; NCBI, National Center for Biotechnology Information; GFF, general-feature-format.

abstract:
  An estimated 17% of cancers worldwide are associated with infectious causes. The extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using human transcriptome (RNA-seq) data from tumor samples. We present an open source bioinformatics pipeline viGEN, which allows for not only the detection and quantification of viral RNA, but also variants in the viral transcripts. The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups. The fourth module calls variants in these viruses. To the best of our knowledge, there are no publicly available pipelines or packages that would provide this type of complete analysis in one open source package. In this paper, we applied the viGEN pipeline to two case studies. We first demonstrate the working of our pipeline on a large public dataset, the TCGA cervical cancer cohort. In the second case study, we performed an in-depth analysis on a small focused study of TCGA liver cancer patients. In the latter cohort, we performed viral-gene quantification, viral-variant extraction and survival analysis. This allowed us to find differentially expressed viral-transcripts and viral-variants between the groups of patients, and connect them to clinical outcome. From our analyses, we show that we were able to successfully detect the human papilloma virus among the TCGA cervical cancer patients. We compared the viGEN pipeline with two metagenomics tools and demonstrate similar sensitivity/specificity. We were also able to quantify viral-transcripts and extract viral-variants using the liver cancer dataset. The results presented corresponded with published literature in terms of rate of detection, and impact of several known variants of HBV genome. This pipeline is generalizable, and can be used to provide novel biological insights into microbial infections in complex diseases and tumorigeneses. Our viral pipeline could be used in conjunction with additional type of immuno-oncology analysis based on RNA-seq data of host RNA for cancer immunology applications. The source code, with example data and tutorial is available at: https://github.com/ICBI/viGEN/.


id: cord-004501-guiy89x8
title: Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers
author: Cojocaru, Florina-Daniela
date: 2020-02-18
txt: ./txt/cord-004501-guiy89x8.txt
cache: ./cache/cord-004501-guiy89x8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076512/
doi: 10.3390/pharmaceutics12020171
summary:
  According to the literature data results, namomaterials designed with different shapes and morphologies display numerous advantages for use in antiviral therapy, namely: nanometric size that permits drug delivery through impermeable barriers [88] , large surface area to volume ratios for large drug payloads incorporation [117] and improved efficacy, surface modification and/or backbone functionalization versatility that facilitates cellular membranes passage [118] or enhancing stability and bioavailability [119] , virucidal activity against a series of viruses (HIV, HSV, HBV, etc.) due to biomimetic properties [120] , increased specificity, improved antiviral delivery and controlled drug release to the target [121] through engineered moieties, decrease the emergence of drug resistance, personalized therapy possibility, protection of the drugs and low adverse drug side effects mainly due to the composition.

abstract:
  Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics.


id: cord-006129-5rog0s98
title: Exploiting the Therapeutic Potential of MicroRNAs in Viral Diseases: Expectations and Limitations
author: Hemida, Maged Gomaa
date: 2012-08-16
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099301/
doi: 10.1007/bf03256383
abstract:
  New therapeutic approaches are urgently needed for serious diseases, including cancer, cardiovascular diseases, viral infections, and others. A recent direction in drug development is the utilization of nucleic acidbased therapeutic molecules, such as antisense oligonucleotides, ribozymes, short interfering RNA (siRNA), and microRNA (miRNA). miRNAs are endogenous, short, non-coding RNA molecules. Some viruses encode their own miRNAs, which play pivotal roles in viral replication and immune evasion strategies. Conversely, viruses that do not encode miRNAs may manipulate host cell miRNAs for the benefits of their replication. miRNAs have therefore become attractive tools for the study of viral pathogenesis. Lately, novel therapeutic strategies based on miRNA technology for the treatment of viral diseases have been progressing rapidly. Although this new generation of molecular therapy is promising, there are still several challenges to face, such as targeting delivery to specific tissues, avoiding off-target effects of miRNAs, reducing the toxicity of the drugs, and overcoming mutations and drug resistance. In this article, we review the current knowledge of the role and therapeutic potential of miRNAs in viral diseases, and discuss the limitations of these therapies, as well as strategies to overcome them to provide safe and effective clinical applications of these new therapeutics.


id: cord-006450-si5168pb
title: Which patients should be tested for viruses on bronchoalveolar lavage fluid?
author: Jouneau, S.
date: 2012-12-14
txt: ./txt/cord-006450-si5168pb.txt
cache: ./cache/cord-006450-si5168pb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101843/
doi: 10.1007/s10096-012-1791-7
summary:
  The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p < 0.01 for each comparison). The variables significantly associated with positive viral tests on univariate analysis were immunosuppression (i.e., HIV infection, corticosteroids >10 mg/day for ≥3 weeks, and/or other immunosuppressive therapy), ground-glass attenuations on chest CT scans, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) ICU stay, and (iii) mechanical ventilation before BAL was performed (p<0.01 for each comparison). This advocates for the systematic use of PCR techniques for viral tests in BALF, in accordance with previous studies [27, 28] , in the situations where viruses may reasonably be suspected (i.e., acute lower tract respiratory disease in immunocompromised patients and/or patients with unexplained bilateral ground-glass attenuations on CT scan).

abstract:
  Bronchoalveolar lavage (BAL) is a major diagnostic tool in lung diseases, including viral respiratory infections. We aimed to better define the situations where viral tests should be performed on BAL fluid (BALF). We retrospectively studied all cases where viral tests [immunofluorescence, immunocytochemistry, viral culture, and/or polymerase chain reaction (PCR)] were performed on BALF during a period of 1 year (2008) in our institution. We compared the characteristics of patients with virus-positive versus virus-negative BALF. Of the 636 BALF samples sent to the microbiology laboratory, 232 underwent viral tests. Of these, 70 (30 %) were positive and identified 85 viruses: herpes simplex virus (HSV)-1 (n = 27), cytomegalovirus (CMV, n = 23), Epstein–Barr virus (EBV, n = 18), human herpesvirus (HHV)-6 (n = 12), respiratory syncytial virus (RSV, n = 3), rhinovirus (n = 1), and adenovirus (n = 1). The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p < 0.01 for each comparison). On multivariate analysis, only immunosuppression [odds ratio (OR) 6.4, 95 % confidence interval (CI) [2.8–14.3], p < 0.0001] and ground-glass attenuations (OR 3.7, 95 % CI [1.8–7.7], p = 0.0004) remained associated with virus-positive BAL. None of the viral tests performed on BALF for the initial assessment of diffuse infiltrative lung disease (n = 15) was positive. PCR improved the diagnostic yield of viral tests on BALF by 50 %. Testing for viruses on BALF should be mostly restricted to immunocompromised patients with acute respiratory diseases and/or patients with unexplained ground-glass attenuations on CT scanning.


id: cord-007255-jmjolo9p
title: Ability to replicate in the cytoplasm predicts zoonotic transmission of livestock viruses
author: Pulliam, Juliet R. C.
date: 2009-02-15
txt: ./txt/cord-007255-jmjolo9p.txt
cache: ./cache/cord-007255-jmjolo9p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110041/
doi: 10.1086/596510
summary:
  The database contains information on the 3 molecular characteristics hypothesized to influence the potential of a virus to cross host species: site of replication (X SR ; whether replication is completed in the cytoplasm or requires nuclear entry), genomic material (X GM ; RNA or DNA), and segmentation of the viral genome (X Seg ; segmented or nonsegmented). Hypothesis testing allowed us to determine how likely it was that the observed patterns were due to chance, whereas model-based prediction allowed us to determine what trait or set of traits was the best predictor of a livestock virus''s ability to infect humans and to estimate the probability that a particular virus species would be able to jump host species, given knowledge of the traits of interest. To examine the magnitude and relative importance of the effects that the 3 molecular characteristics of interest have on the ability of the viral species in the database to infect humans, we developed a set of logistic regression models.

abstract:
  Understanding viral factors that promote cross-species transmission is important for evaluating the risk of zoonotic emergence. Weconstructed a database of viruses of domestic artiodactyls and examined the correlation between traits linked in the literature to cross-species transmission and the ability of viruses to infect humans. Among these traits-genomic material, genome segmentation, and replication without nuclear entry-the last is the strongest predictor of cross-species transmission. This finding highlights nuclear entry as a barrier to transmission and suggests that the ability to complete replication in the cytoplasm may prove to be a useful indicator of the threat of cross-species transmission.


id: cord-009101-376snefs
title: Viral Infections of the Newborn
author: Strodtbeck, Frances
date: 2015-12-16
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135601/
doi: 10.1111/j.1552-6909.1995.tb02548.x
abstract:
  Viral infections of the newborn result in significant morbidity and mortality each year. The fetus and newborn are particularly wlnerable to viral infection. The range of expression may vary from no clinical disease to devastating illness and infection occurring before, during, or after birth. Nursing management is determined by the specific viral infection, the severity of the illness, and the unique conditions of the newborn and his/her family. Promising new therapies are on the horizon that may lessen the severity of viral disease. Until such time, the major thrusts of management of neonatal viral disease are prevention of infection and supportive care for the acutely ill newborn.


id: cord-009577-29u7pdpk
title: Molecular pathogenesis of neurotropic viral infections
author: Gonzalez‐Scarano, F.
date: 2004-10-08
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159691/
doi: 10.1002/ana.410220502
abstract:
  Classical virologists defined a number of viruses that affect the nervous system and identified tissue tropism, extraneural replication, and viremia as important parameters that determine whether viral infections will affect the central nervous system. Molecular techniques are expanding this knowledge by permitting us to relate specific genes and gene products to two defined phenotypes: neuroinvasion and neurovirulence. Two converging situations make this knowledge particularly useful: (1) the development of antiviral drugs and subunit vaccines, which mandate that pathogenesis be related to specific regions of the viral genome; and (2) the expanding problem of central nervous system infections in immunodeficient states.


id: cord-010233-772e35kx
title: Respiratory illness caused by picornavirus infection: a review of clinical outcomes
author: Monto, Arnold S.
date: 2002-01-03
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172950/
doi: 10.1016/s0149-2918(01)80133-8
abstract:
  Background: Respiratory infections result from invasion of the respiratory tract, mainly by viruses, and are the leading cause of acute morbidity in individuals of all ages worldwide. During peak season, picornaviruses cause 82% of all episodes of acute nasopharyngitis (the common cold), the most frequent manifestation of acute respiratory infection, and produce more restriction of activity and physician consultations annually than any other viral or bacterial source of respiratory illness. Objective: This article reviews the clinical impact and outcomes of picornavirus-induced respiratory infections in specific populations at risk for complications. It also discusses the potential economic impact of the morbidity associated with picornavirus-induced respiratory infection. Methods: Relevant literature was identified through searches of MEDLINE, OVID, International Pharmaceutical Abstracts, and Lexis-Nexis. The search terms used were picornavirus, rhinovirus, enterovirus, viral respiratory infection, upper respiratory infection, disease burden, economic, cost, complications, asthma, COPD, immunocompromised, elderly, otitis media, and sinusitis. Additional publications were identified from the reference lists of the retrieved articles. Conclusions: Based on the clinical literature, picornavirus infections are associated with severe morbidity as well as considerable economic and societal costs. Future research should focus on identifying patterns of illness and the costs associated with management of these infections. New treatments should be assessed not only in terms of their ability to produce the desired clinical outcome, but also in terms of their ability to reduce the burden of disease, decrease health care costs, and improve productivity.


id: cord-011095-79ce5900
title: Respiratory Virus Co-infection in Acute Respiratory Infections in Children
author: Meskill, Sarah D.
date: 2020-01-24
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223550/
doi: 10.1007/s11908-020-0711-8
abstract:
  PURPOSE OF REVIEW: This investigation aims to understand the role and burden of viral co-infections for acute respiratory illnesses in children. Co-infection can be either viral-viral or viral-bacterial and with new technology there is more information on the role they play on the health of children. RECENT FINDINGS: With the proliferation of multiplex PCR for rapid diagnosis of multiple viruses as well as innovations on identification of bacterial infections, research has been attempting to discover how these co-infections affect each other and the host. Studies are aiming to discern if the epidemiology of viruses seen at a population level is related to the interaction between different viruses on a host level. Studies are also attempting to discover the burden of morbidity and mortality of these viral-viral co-infections on the pediatric population. It is also becoming important to understand the interplay of certain viruses with specific bacteria and understanding the impact of viral-bacterial co-infections. SUMMARY: RSV continues to contribute to a large burden of disease for pediatric patients with acute respiratory illnesses. However, recent literature suggests that viral-viral co-infections do not add to this burden and might, in some cases, be protective of severe disease. Viral-bacterial co-infections, on the other hand, are most likely adding to the burden of morbidity in pediatric patients because of the synergistic way they can infect the nasopharyngeal space. Future research needs to focus on confirming these conclusions as it could affect hospital cohorting, role of molecular testing, and therapeutic interventions.


id: cord-015893-e0fofgxq
title: Viral Disease, Air Pollutants, Nanoparticles, and Asthma
author: Ryhal, Bruce
date: 2011-05-03
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119993/
doi: 10.1007/978-1-4419-6836-4_11
abstract:
  Health care providers who treat patients with respiratory disease are often asked by their patients, “What caused my asthma? And what causes my asthma suddenly to become worse?” These questions have always been difficult to answer, and moving directly to a discussion of the management of asthma is a much easier road to take. In recent years, though, enough information has accumulated about the causes of asthma that one can weave a story containing useful advice that may help patients participate in the management of their disease. And there are also recent studies that can provide answers to the questions posed by physicians who have watched in puzzlement as their previously well-controlled asthma patients have spiraled rapidly out of control. This story has been growing increasingly complex, with an ever-expanding cast of players that sometimes creates a tangled web of interactions.


id: cord-016475-7ldxvbpz
title: Anti-viral approaches against influenza viruses
author: Pleschka, Stephan
date: 2006
txt: ./txt/cord-016475-7ldxvbpz.txt
cache: ./cache/cord-016475-7ldxvbpz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120762/
doi: 10.1007/978-0-387-31047-3_5
abstract: nan
summary:
  After influenza virus infection antibodies directed against all major viral proteins can be detected in humans and the level of serum antibodies correlate with resistance to disease (Couch, 2003; Couch and Kasel, 1983; Coulter et al., 2003; Nichol et al., 1998; Potter and Oxford, 1979) . Nevertheless, IKK and NFκB might not only have anti-viral functions as two recent studies demonstrate that influenza viruses replicate much better in cells where NFκB is pre-activated (Nimmerjahn et al., 2004; Wurzer et al., 2004) . Apoptosis is mainly regarded to be a host cell defense against virus viruses (reviewed in: Julkunen et al., 2000; Ludwig et al., 2003; infections since many viruses express anti-apoptotic proteins to prevent this cellular response. Influenza virus-induced NF-kappaB-dependent gene expression is mediated by overexpression of viral proteins and involves oxidative radicals and activation of IkappaB kinase


id: cord-016499-5iqpl23p
title: Rhinoviruses
author: Mackay, Ian M.
date: 2014-02-27
txt: ./txt/cord-016499-5iqpl23p.txt
cache: ./cache/cord-016499-5iqpl23p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120790/
doi: 10.1007/978-1-4899-7448-8_29
summary:
  A convenience population of 15 healthy children (1-9 years old) without asthma were followed during at least three seasons, and picornaviruses were detected in 5 % of 740 specimens (21 % of infections) not associated with symptoms, The impact of HRV typing and of sampling based only on symptoms. Clinical features and complete genome characterization of a distinct human rhinovirus genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children Comparison of results of detection of rhinovirus by PCR and viral culture in human nasal wash specimens from subjects with and without clinical symptoms of respiratory illness Detection of human rhinovirus C viral genome in blood among children with severe respiratory infections in the Philippines

abstract:
  Picornaviruses, which include the human rhinoviruses (HRVs) and enteroviruses (EVs), are the most frequent cause of acute human illness worldwide. HRVs are the most prevalent cause of acute respiratory tract illnesses (ARIs) which usually commence in the upper respiratory tract (URT). ARIs are the leading cause of morbidity in children under 5 years and occur in all seasons. ARIs linked to HRV infections are associated with excessive and perhaps inappropriate antibiotic prescribing and with significant direct and indirect healthcare expenditure. ARI incidence is highest in the first 2 years of life, with up to thirteen episodes per year including up to six positive for an HRV, and it is not uncommon to average one infection per child-month.


id: cord-016798-tv2ntug6
title: Bioinformatics Applications in Advancing Animal Virus Research
author: Gautam, Ablesh
date: 2019-06-06
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121192/
doi: 10.1007/978-981-13-9073-9_23
abstract:
  Viruses serve as infectious agents for all living entities. There have been various research groups that focus on understanding the viruses in terms of their host-viral relationships, pathogenesis and immune evasion. However, with the current advances in the field of science, now the research field has widened up at the ‘omics’ level. Apparently, generation of viral sequence data has been increasing. There are numerous bioinformatics tools available that not only aid in analysing such sequence data but also aid in deducing useful information that can be exploited in developing preventive and therapeutic measures. This chapter elaborates on bioinformatics tools that are specifically designed for animal viruses as well as other generic tools that can be exploited to study animal viruses. The chapter further provides information on the tools that can be used to study viral epidemiology, phylogenetic analysis, structural modelling of proteins, epitope recognition and open reading frame (ORF) recognition and tools that enable to analyse host-viral interactions, gene prediction in the viral genome, etc. Various databases that organize information on animal and human viruses have also been described. The chapter will converse on overview of the current advances, online and downloadable tools and databases in the field of bioinformatics that will enable the researchers to study animal viruses at gene level.


id: cord-018058-n3majqes
title: Historical Overview
author: Modrow, Susanne
date: 2013-08-12
txt: ./txt/cord-018058-n3majqes.txt
cache: ./cache/cord-018058-n3majqes.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122844/
doi: 10.1007/978-3-642-20718-1_1
summary:
  Many of the steps that characterize a viral infection were first discovered in experiments with bacterial viruses: such processes include attachment and penetration, the reproduction-cycledependent regulation of gene expression that results in early and late synthesized proteins, and lysogeny, which is associated with the existence of prophages. Besides the importance for tumour virus research, these observations aroused interest in the question concerning the basis of the high susceptibility of newborn animals to viral infections, and suggested investigations on the innate resistance of an organism to infections as well as the time and the causes of its formation. Between 1918 and 1920, a pandemic emerging viral disease, Spanish flu, claimed more than 20 million lives, i.e., more than in the First World War. After cultivation of the virus responsible in embryonated chicken eggs in 1933, their haemagglutinating properties were discovered in 1941 (i.e., their ability to agglutinate red blood cells), thereby laying the basis for the development of haemagglutination tests to detect viruses.

abstract:
  “Poisons” were originally considered as the causative agents of illnesses that we know as viral diseases today. At that time, there were no standard methods to detect pathogenic (disease-causing) organisms such as bacteria and protozoa in the supposed “poisonous materials”. Only animal experiments performed by Louis Pasteur at the end of the nineteenth century, in which no dilution of the poisonous properties was achieved even after several passages, suggested that the disease-causing agent was able to multiply in the organism. Therefore, there was talk of a reproducible “virus” (Latin for “poison” or “slime”) in living organisms, and later also in cells. In St. Petersburg in 1892, Dimitri I. Ivanovski demonstrated that tobacco mosaic disease is caused by an “ultrafilterable” agent, whose size is significantly smaller than that of bacteria: tobacco mosaic virus (bacteria filters have a pore size of approximately 0.2 μm, however, most viruses are smaller than 0.1 μm). Soon afterwards, Martinus Willem Beijerinck came to the same conclusion: he developed, for the first time, the notion of a self-replicating, “liquid” agent (contagium vivum fluidum). The discovery of foot-and-mouth disease virus by Friedrich Loeffler and Paul Frosch in Greifswald in 1898 was the first evidence of an animal pathogenic virus.


id: cord-018325-k69h9cc5
title: Acute Viral Rhinitis
author: Çatlı, Tolgahan
date: 2019-05-14
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123171/
doi: 10.1007/978-3-030-21217-9_23
abstract:
  Rhinitis refers to any kind of inflammatory condition of the nasal mucosal linings. Generally, acute rhinitis is associated with environmental allergies or respiratory viral infections. Viral microbes with numerous types and subtypes can infect the respiratory epithelium of the nasal cavity in a repetitive fashion throughout the year, or during a specific period of time such as winter or fall. Among all forms of inflammatory diseases of the nasal mucosa, acute viral rhinitis (AVR) has unique epidemiological, clinical, and therapeutic characteristics. As the most prevalent type of rhinitis, AVR is also the most common form of any infectious disease of the human body. Although it is almost always self-limiting, in rare circumstances disease might progress and the clinical scenario could become complicated. Common complaints and physical findings related to AVR are similar to those seen with other types of rhinitis such as allergic, hormonal, senile, or drug induced. The clinician must interpret these symptoms and findings in the context of other parameters such as “duration, environmental factors, and patient characteristics” to establish an accurate diagnose and appropriate therapeutic management. In this chapter, we aim to discuss the epidemiology, pathogenesis, clinical findings, differential diagnosis, and therapeutic management of AVR in light of the recent literature knowledge. It is our hope that this chapter may aid medical professionals who encounter AVR in daily practice.


id: cord-018430-u3k8pds6
title: Myocarditis
author: Mason, Jay W.
date: 2007
txt: ./txt/cord-018430-u3k8pds6.txt
cache: ./cache/cord-018430-u3k8pds6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123303/
doi: 10.1007/978-1-84628-715-2_62
summary:
  The classification states that "myocarditis is diagnosed by established histological, immunological and immunohistochemical criteria." The Dallas criteria 5 provide consensus-derived histologic criteria: "an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of ischemic damage associated with coronary artery disease." However, many have speculated that less pronounced histologic abnormalities may be present and that additional molecular, immunologic, and immunohistochemical diagnostic criteria can be used productively. 330 These criteria define active myocarditis (see also Fig. 59 .7A) as "an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of ischemic damage associated with coronary artery disease." Furthermore, other causes of inflammation (e.g., connective tissue disorders, infection, drugs) should be excluded. 392 An interesting hypothesis to explain the high frequency of dilated heart muscle disease is the presence of myocarditis in HIV-infected patients with left ventricular dysfunction. The ECG abnormalities suggesting myocardial involvement are present in a high proportion of patients, 414 but clinical evidence of cardiac dysfunction occurs in only 10% to 25% of cases.

abstract:
  Viruses are the most common cause of myocarditis in economically advanced countries. Enteroviruses and adenoviruses are the most common etiologic agents. Viral myocarditis is a triphasic process. Phase 1 is the period of active viral replication in the myocardium during which the symptoms of myocardial damage range from none to cardiogenic shock. If the disease process continues, it enters phase 2, which is characterized by autoimmunity triggered by viral and myocardial proteins. Heart failure often appears for the first time in phase 2. Phase 3, dilated cardiomyopathy, is the end result in some patients. Diagnostic procedures and treatment should be tailored to the phase of disease. Viral myocarditis is a significant cause of dilated cardiomyopathy, as proved by the frequent presence of viral genomic material in the myocardium, and by improvement in ventricular function by immunomodulatory therapy. Myocarditis of any etiology usually presents with heart failure, but the second most common presentation is ventricular arrhythmia. As a result, myocarditis is one of the most common causes of sudden death in young people and others without preexisting structural heart disease. Myocarditis can be definitively diagnosed by endomyocardial biopsy. However, it is clear that existing criteria for the histologic diagnosis need to be refined, and that a variety of molecular markers in the myocardium and the circulation can be used to establish the diagnosis. Treatment of myocarditis has been generally disappointing. Accurate staging of the disease will undoubtedly improve treatment in the future. It is clear that immunosuppression and immunomodulation are effective in some patients, especially during phase 2, but may not be as useful in phases 1 and 3. Since myocarditis is often selflimited, bridging and recovery therapy with circulatory assistance may be effective. Prevention by immunization or receptor blocking strategies is under development. Giant cell myocarditis is an unusually fulminant form of the disease that progresses rapidly to heart failure or sudden death. Rapid onset of disease in young people, especially those with other autoimmune manifestations, accompanied by heart failure or ventricular arrhythmias, suggests giant cell myocarditis. Peripartum cardiomyopathy in economically developed countries is usually the result of myocarditis.


id: cord-018526-rz7id5mt
title: Non-viral Vector for Muscle-Mediated Gene Therapy
author: Braun, Serge
date: 2018-12-14
txt: ./txt/cord-018526-rz7id5mt.txt
cache: ./cache/cord-018526-rz7id5mt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123420/
doi: 10.1007/978-3-030-03095-7_9
summary:
  Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies. In humans, intramuscular injections of naked plasmid encoding angiogenic factors (such as VEGF165 or HGF) were used in small numbers of patients with critical limb ischemia and did demonstrate promising clinical efficacy for the treatment of peripheral arterial disease. A meta-analysis of 12 clinical trials (1494 patients total) of local administration of pro-angiogenic growth factors (VEGF, FGF, HGF, Del-1, HIF-1alpha) using plasmid or viral gene transfer by intra-arterial or intramuscular injections showed that, despite promising results in single studies, no clear benefit could be identified in peripheral artery disease patients, irrespective of disease severity [51] .

abstract:
  Non-viral gene delivery to skeletal muscle was one of the first applications of gene therapy that went into the clinic, mainly because skeletal muscle is an easily accessible tissue for local gene transfer and non-viral vectors have a relatively safe and low immunogenic track record. However, plasmid DNA, naked or complexed to the various chemistries, turn out to be moderately efficient in humans when injected locally and very inefficient (and very toxic in some cases) when injected systemically. A number of clinical applications have been initiated however, based on transgenes that were adapted to good local impact and/or to a wide physiological outcome (i.e., strong humoral and cellular immune responses following the introduction of DNA vaccines). Neuromuscular diseases seem more challenging for non-viral vectors. Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies.


id: cord-020235-stcrozdw
author: nan
date: 2012-03-15
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134445/
doi: 10.1016/s0174-3031(82)80128-5
abstract: nan
title:
  Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981


id: cord-022156-mm8en4os
title: Tracheal Infections
author: Isaiah, Amal
date: 2015-07-14
txt: ./txt/cord-022156-mm8en4os.txt
cache: ./cache/cord-022156-mm8en4os.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153446/
doi: 10.1007/978-3-319-21744-4_12
summary:
  Tracheal infections have a signifi cantly lower incidence compared to infections of the upper respiratory tract, with 1-5 % of all children requiring outpatient evaluation for viral croup within the fi rst 3 years of life. In 1958, the fi rst evidence for association between croup and two newly isolated myxoviruses, parainfl uenza virus types 1 and 2, resulted in separation of two categories of cases-mild, requiring only outpatient follow up, and severe, requiring hospitalization [ 12 ] . Among other important viral pathogens causing tracheal infections, RSV was studied in isolates from sentinel practices in England and Wales from 1975 to 1990, during which an increase in mortality, by as much as 60-80 %, was observed in comparison with parainfl uenza and infl uenza viruses [ 13 ] . [ 31 ] studied the clinical courses of croup caused by parainfl uenza and infl uenza viruses to highlight the differences in morbidity caused by the different viral strains in hospitalized children.

abstract:
  Infectious processes of the trachea represent a distinct clinical entity with an evolving landscape owing to advances in airway management and vaccination practices. Untreated inflammatory processes of the trachea may present in the form of acute airway obstruction, potentially resulting in significant morbidity and even mortality. Therefore it is important to recognize the cardinal features of some of the common tracheal infectious processes to differentiate them from non-infectious pathology, as the latter is associated with a more indolent course. As with most other infectious processes of the airway, pathogens causing tracheal infection can be bacterial, viral or fungal in nature. Viral etiology represents the most common cause of laryngotracheal infection in a child. Bacterial infections of the trachea are responsible for more significant morbidity, including prolonged hospitalization, need for endotracheal intubation and even an occasional tracheostomy. The current chapter describes the clinical features and microbiology of tracheal infections at large, explores the utility of diagnostic tests, and provides an algorithm for management.


id: cord-022196-1tionxun
title: The Nature and Classification of Animal Viruses
author: FENNER, FRANK
date: 2013-11-17
txt: ./txt/cord-022196-1tionxun.txt
cache: ./cache/cord-022196-1tionxun.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155428/
doi: 10.1016/b978-0-12-253040-1.50006-3
abstract: nan
summary:
  With most isometric particles and in all complex virions, the capsid encloses another protein structure containing the viral genome, called the core. All animal viruses with tubular nucleocapsids are enveloped, and in these the lipid layer from which glycoprotein peplomers project is probably applied to a protein shell (the membrane protein; see Fig. 1 -1), which may be relatively rigid, as in Rhabdovirus, or readily distorted (as in the myxoviruses) so that in negatively stained electron micrographs the virions appear to be pleomorphic. The RNA viruses that have the largest (single-stranded) genomes, those of the Leukovirus genus, also have a highly complex structure with an envelope enclosing an icosahedral capsid that, in turn, surrounds a tubular nucleocapsid. The conventional physicochemical criteria [(a) nucleic acid: type, strandedness, fragmentation, and molecular weight; (b) virion: shape, size, and symmetry] are suitable for classification at this level of family/genus, perhaps assisted by the serological cross-reactivity of "group" antigens where these have been recognized.


id: cord-022349-z8w1wkm8
title: Human and Animal Viruses
author: Beeler, Judy A.
date: 2007-09-02
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155599/
doi: 10.1016/b978-012361946-4/50010-7
abstract:
  This chapter provides an overview of the human and animal viruses. Viruses held to a low number of passages in animals or cell cultures represent a viral population that is similar to that found in nature, and freezing these pools guards against genetic mutations that occur during subsequent passage. Aliquots of viral stocks frozen at a designated passage level can then be used for multiple and repeatable experiments with the same viral population. Furthermore, it is important that consistency should be maintained during the production of viral vaccines; new lots of final product are prepared with frozen viral seed stocks that consistently reproduce the desired immunogenic and attenuation characteristics. To better appreciate the requirements for freezing and freeze drying of human and animal viruses, some consideration is given to understanding the structural and functional organization of this diverse group of microorganisms. The classification of viruses is based on morphological and physiochemical properties. Thus, viruses are divided into those with DNA or RNA genomes and subdivided into families based on size and structural properties. Several methods for preservation of viruses are included in the chapter.


id: cord-023143-fcno330z
title: Molecular aspects of viral immunity
author: nan
date: 2004-02-19
txt: ./txt/cord-023143-fcno330z.txt
cache: ./cache/cord-023143-fcno330z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167094/
doi: 10.1002/jcb.240591009
abstract: nan
summary:
  Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells.


id: cord-023705-3q9yr6np
title: Viral Replication
author: FENNER, FRANK
date: 2014-06-27
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173495/
doi: 10.1016/b978-0-12-253055-5.50008-6
abstract:
  Viral replication is the central focus of much experimental virology and is a significant part of molecular biology. Studies with bacteriophages in their prokaryotic host cells in the 1940s and 1950s provided the first insights into the complexities of viral replication. With the development of mammalian cell culture procedures, the techniques used for the study of bacteriophages were adapted to animal viruses. Progress has been such that the basic mechanisms of transcription, translation, and nucleic acid replication have been characterized for all the major families of animal viruses and the strategy of gene expression and its regulation clarified. Many important biochemical phenomena such as the splicing and other types of posttranscriptional processing of RNA, the posttranslational cleavage and glycosylation of proteins, the replication of RNA, reverse transcription, integration, and the transposition of viral genes and cellular oncogenes were first elucidated by virologists and have general application in cell biology. The chapter provides a general overview on viral replication for understanding pathogenesis, immunity, chemotherapy, and the role of viruses in cancer.


id: cord-023731-jqgervt7
title: Laboratory Diagnosis of Viral Diseases
author: FENNER, FRANK
date: 2014-06-27
txt: ./txt/cord-023731-jqgervt7.txt
cache: ./cache/cord-023731-jqgervt7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173550/
doi: 10.1016/b978-0-12-253055-5.50017-7
summary:
  Having allocated it to a particular family (e.g., Adenoviridae), one can then go on to determine the species or serotype (e.g., canine Immunodiffusion Antibody neutralizes infectivity of virion; inhibits cytopathology, reduces plaques, or protects animals Antibody inhibits viral hemagglutination Antigen-antibody complex binds complement, which is thereafter unavailable for the lysis of hemolysissensitized sheep red blood cells Antibody-aggregated virions are visible by electron microscopy Antibody labeled with fluorochrome binds to intracellular antigen; fluoresces by UV microscopy Peroxidase-labeled antibody binds to intracellular antigen; colored precipitate forms on adding substrate Enzyme-labeled antibody (or antigen) binds to antigen (or antibody); substrate changes color Radiolabeled antibody (or antigen) binds to antigen (or antibody), e.g., attached to solid phase Antibodies and soluble antigens produce visible lines of precipitate in a gel adenovirus 1) by more discriminating serological procedures.

abstract:
  Tests for the specific diagnosis of a viral infection in an animal are of two general types: (1) those that demonstrate the presence of the virus and (2) those that demonstrate the presence of specific viral antibody. The provision, by a single laboratory, of a comprehensive service for the diagnosis of viral infections of domestic animals is a formidable undertaking. There are about 200 individual viral species in some 20 different viral families that infect the eight major domestic animal species. If antigenic types within an individual viral species are considered and the number of animal species is broadened to include turkey, duck, and zoo and laboratory animals, then the number of individual viruses exceeds 1000. It is, therefore, not surprising that few single laboratories could have available the necessary specific reagents, skills, and experience for the diagnosis of such a large number of infections.


id: cord-103460-5thh6syt
title: Climate change will drive novel cross-species viral transmission
author: Carlson, Colin J.
date: 2020-07-14
url: https://doi.org/10.1101/2020.01.24.918755
doi: 10.1101/2020.01.24.918755
abstract:
  At least 10,000 species of mammal virus are estimated to have the potential to spread in human populations, but the vast majority are currently circulating in wildlife, largely undescribed and undetected by disease outbreak surveillance1,2,3. In addition, changing climate and land use are already driving geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species4,5. In some cases, this will inevitably facilitate spillover into humans6,7—a possible mechanistic link between global environmental change and emerging zoonotic disease8. Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of geographic range shifts for 3,870 mammal species under climate change and land use scenarios for the year 2070. Range-shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, driving the cross-species transmission of novel viruses at least 4,000 times. Counter to expectations, holding warming under 2°C within the century does not reduce new viral sharing, due to greater range expansions—highlighting the need to invest in surveillance even in a low-warming future. Most projected viral sharing is driven by diverse hyperreservoirs (rodents and bats) and large-bodied predators (carnivores). Because of their unique dispersal capacity, bats account for the majority of novel viral sharing, and are likely to share viruses along evolutionary pathways that could facilitate future emergence in humans. Our findings highlight the urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking range shifts, especially in tropical countries that harbor the most emerging zoonoses.


id: cord-252763-gy8f1oyt
title: Viral Diarrhoea in a Rural Coastal Region of Karnataka India
author: Shetty, Mamatha
date: 1995-10-17
txt: ./txt/cord-252763-gy8f1oyt.txt
cache: ./cache/cord-252763-gy8f1oyt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/tropej/41.5.301
doi: 10.1093/tropej/41.5.301
summary:
  A total of 106 children below 5 years of age admitted to the Kasturba Medical College Hospital Manipal Karnataka (South India) were investigated over a period of 6 months to determine the aetiologkal role of viruses in acute diarrhoea. 1 " 3 In view of the recent recognition of some viral aetiological agents of acute infantile diarrhoea, we conducted the present study to identify viruses as the causative agents of infantile diarrhoea in Manipal, a place in Coastal Karanataka (South India). One-hundred-and-six children aged below 5 years, suffering from acute watery diarrhoea of less than 4 days'' duration who attended the out patient clinic of paediatric dept of the Kasturba Medical College Hospital, Karanataka, South India were included in the study. Enteric adenoviruses are well established as respiratory viruses and are second to Rotavirus as the most common cause of pediatric viral gastroenteritis.

abstract:
  Abstract. A total of 106 children below 5 years of age admitted to the Kasturba Medical College Hospital Manipal Karnataka (South India) were investigated over a period of 6 months to determine the aetiologkal role of viruses in acute diarrhoea. Viral aetiological agents isolated were Rotaviruses in 12 (11 per cent) cases, Adenoviruses in 3 (3 per cent) cases, corona virus and astroviruses in two (2 per cent) cases each. Non-viral isolates were Cryptosporidium and Salmonella typhimurium in two cases each, and Entamoeba histolyticaand and Shigella flexneri in one case each.


id: cord-254194-962vynwk
title: Silver Nanoparticles as Potential Antiviral Agents
author: Galdiero, Stefania
date: 2011-10-24
url: https://doi.org/10.3390/molecules16108894
doi: 10.3390/molecules16108894
abstract:
  Virus infections pose significant global health challenges, especially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the production of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.


id: cord-254478-scc9wee0
author: To, Kelvin Kai-Wang
date: 2020-03-23
txt: ./txt/cord-254478-scc9wee0.txt
cache: ./cache/cord-254478-scc9wee0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32213337/
doi: 10.1016/s1473-3099(20)30196-1
summary:
  title: Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. We present findings of an observational cohort study of the temporal profile of viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from posterior oropharyngeal saliva samples and serum antibody responses, dated by symptom onset and correlated with clinical findings.

title:
  Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

abstract:
  BACKGROUND: Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. METHODS: We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. FINDINGS: Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log(10) copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R(2)=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R(2)>0·9). No genome mutations were detected on serial samples. INTERPRETATION: Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. FUNDING: Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.


id: cord-258685-ayek8zbo
author: Har-Noy, Michael
date: 2020-05-12
txt: ./txt/cord-258685-ayek8zbo.txt
cache: ./cache/cord-258685-ayek8zbo.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12967-020-02363-3
doi: 10.1186/s12967-020-02363-3
summary:
  Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ''Disease X''. The lysis of viral infected cells by activated innate effector cells and cross-reactive allo-specific memory CTL releases "danger signals" [18] and heat shock proteins (HSP) [19] which chaperone viral antigens (e.g., GRP78, HSP70) [20, 21] into the microenvironment, creating the conditions for "in situ vaccination", which leads to development of viral-specific cellular immunity. Modulating the immune system of elderly individuals through alloantigen priming to provide high titers of non-exhausted Th1/ CTL memory cells that can be non-specifically activated upon encounter with any virus to cause release type 1 cytokines may provide an immediate anti-viral immune response upon viral exposure and could also reinstate responsiveness to viral vaccines [85] .

title:
  Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

abstract:
  BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim(®)) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim(®) creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter. CONCLUSION: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.


id: cord-259233-smmhhroe
title: Membrane dynamics associated with viral infection
author: de Armas‐Rillo, Laura
date: 2016-01-28
url: https://www.ncbi.nlm.nih.gov/pubmed/26817660/
doi: 10.1002/rmv.1872
abstract:
  Viral replication and spreading are fundamental events in the viral life cycle, accounting for the assembly and egression of nascent virions, events that are directly associated with viral pathogenesis in target hosts. These processes occur in cellular compartments that are modified by specialized viral proteins, causing a rearrangement of different cell membranes in infected cells and affecting the ER, mitochondria, Golgi apparatus, vesicles and endosomes, as well as processes such as autophagic membrane flux. In fact, the activation or inhibition of membrane trafficking and other related activities are fundamental to ensure the adequate replication and spreading of certain viruses. In this review, data will be presented that support the key role of membrane dynamics in the viral cycle, especially in terms of the assembly, egression and infection processes. By defining how viruses orchestrate these events it will be possible to understand how they successfully complete their route of infection, establishing viral pathogenesis and provoking disease. © 2015 The Authors Reviews in Medical Virology Published by John Wiley & Sons, Ltd.


id: cord-260554-nao59qx4
title: Viral fitness: definitions, measurement, and current insights
author: Wargo, Andrew R
date: 2012-09-15
url: https://www.sciencedirect.com/science/article/pii/S1879625712001290
doi: 10.1016/j.coviro.2012.07.007
abstract:
  Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.


id: cord-262585-5vjqrnwh
title: Resources to Discover and Use Short Linear Motifs in Viral Proteins
author: Hraber, Peter
date: 2019-08-16
url: https://www.ncbi.nlm.nih.gov/pubmed/31427097/
doi: 10.1016/j.tibtech.2019.07.004
abstract:
  Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.


id: cord-262753-jld1ygxt
title: Global analysis of polysome-associated mRNA in vesicular stomatitis virus infected cells
author: Neidermyer, William J.
date: 2019-06-21
url: https://www.ncbi.nlm.nih.gov/pubmed/31226162/
doi: 10.1371/journal.ppat.1007875
abstract:
  Infection of mammalian cells with vesicular stomatitis virus (VSV) results in the inhibition of cellular translation while viral translation proceeds efficiently. VSV RNA synthesis occurs entirely within the cytoplasm, where during transcription the viral polymerase produces 5 mRNAs that are structurally indistinct to cellular mRNAs with respect to their 5′ cap-structure and 3′-polyadenylate tail. Using the global approach of massively parallel sequencing of total cytoplasmic, monosome- and polysome-associated mRNA, we interrogate the impact of VSV infection of HeLa cells on translation. Analysis of sequence reads in the different fractions shows >60% of total cytoplasmic and polysome-associated reads map to the 5 viral genes by 6 hours post-infection, a time point at which robust host cell translational shut-off is observed. Consistent with an overwhelming abundance of viral mRNA in the polysome fraction, the reads mapping to cellular genes were reduced. The cellular mRNAs that remain most polysome-associated following infection had longer half-lives, were typically larger, and were more AU rich, features that are shared with the viral mRNAs. Several of those mRNAs encode proteins known to positively affect viral replication, and using chemical inhibition and siRNA depletion we confirm that the host chaperone heat shock protein 90 (hsp90) and eukaryotic translation initiation factor 3A (eIF3A)—encoded by 2 such mRNAs—support viral replication. Correspondingly, regulated in development and DNA damage 1 (Redd1) encoded by a host mRNA with reduced polysome association inhibits viral infection. These data underscore the importance of viral mRNA abundance in the shut-off of host translation in VSV infected cells and link the differential translatability of some cellular mRNAs with pro- or antiviral function.


id: cord-262776-6k7tcgfs
title: Assessment of the viral safety of antivenoms fractionated from equine plasma
author: Burnouf, Thierry
date: 2004-09-30
url: https://www.sciencedirect.com/science/article/pii/S1045105604000223
doi: 10.1016/j.biologicals.2004.07.001
abstract:
  Abstract Antivenoms are preparations of intact or fragmented (F(ab′)2 or Fab) immunoglobulin G (IgG) used in human medicine to treat the severe envenomings resulting from the bites and stings of various animals, such as snakes, spiders, scorpions, or marine animals, or from the contact with poisonous plants. They are obtained by fractionating plasma collected from immunized horses or, less frequently, sheep. Manufacturing processes usually include pepsin digestion at acid pH, papain digestion, ammonium sulphate precipitation, caprylic acid precipitation, heat coagulation and/or chromatography. Most production processes do not have deliberately introduced viral inactivation or removal treatments, but antivenoms have never been found to transmit viruses to humans. Nevertheless, the recent examples of zoonotic diseases highlight the need to perform a careful assessment of the viral safety of antivenoms. This paper reviews the characteristics of equine viruses of antivenoms and discusses the potential of some manufacturing steps to avoid risks of viral contamination. Analysis of production parameters indicate that acid pH treatments and caprylic acid precipitations, which have been validated for the manufacture of some human IgG products, appear to provide the best potential for viral inactivation of antivenoms. As many manufacturers of antivenoms located in developing countries lack the resources to conduct formal viral validation studies, it is hoped that this review will help in the scientific understanding of the viral safety factors of antivenoms, in the controlled implementation of the manufacturing steps with expected impact on viral safety, and in the overall reinforcement of good manufacturing practices of these essential therapeutic products.


id: cord-265900-7lj4bfli
author: Luo, Honglin
date: 2015-09-29
txt: ./txt/cord-265900-7lj4bfli.txt
cache: ./cache/cord-265900-7lj4bfli.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1879625715001406
doi: 10.1016/j.coviro.2015.09.005
summary:
  Several proteins encoded by DNA tumor viruses, such as the human papillomavirus (HPV) E6 and E7 proteins [14, 15] and the adenovirus E1B55k/E4orf6 proteins [16] , have been shown to induce the assembly of an E3 ligase complex that contains both viral protein and cellular E3 to catalyze the ubiquitination of p53 and subsequent degradation by the proteasome. In addition to its pro-viral function usurped by viruses as discussed above, the UPS-mediated cellular protein degradation may also represent a host defense mechanism against viral infection. ISG15 and the ISGylation conjugation system represent an important host defense mechanism against infection of a broad spectrum of viruses, including Sindbis virus, Viral interaction with the host ubiquitin-proteasome system (UPS): pro-viral and anti-viral function of the UPS in viral pathogenesis. The UPS, including modification of key signaling molecules involved in innate immunity by ubiquitin or ubiquitin-like modifiers (e.g. SUMO and ISG15), represents an important host anti-viral defense mechanism.

title:
  Interplay between the virus and the ubiquitin–proteasome system: molecular mechanism of viral pathogenesis

abstract:
  The ubiquitin–proteasome system (UPS) plays a central role in a wide range of fundamental cellular functions by ensuring protein quality control and through maintaining a critical level of important regulatory proteins. Viruses subvert or manipulate this cellular machinery to favor viral propagation and to evade host immune response. The UPS serves as a double-edged sword in viral pathogenesis: on the one hand, the UPS is utilized by many viruses to maintain proper function and level of viral proteins; while on the other hand, the UPS constitutes a host defense mechanism to eliminate viral components. To combat this host anti-viral machinery, viruses have evolved to employ the UPS to degrade or inactivate cellular proteins that limit viral growth. This review will highlight our current knowledge pertaining to the different roles for the UPS in viral pathogenesis.


id: cord-266147-s8rxzm0t
title: Modern Plasma Fractionation
author: Burnouf, Thierry
date: 2007-03-28
txt: ./txt/cord-266147-s8rxzm0t.txt
cache: ./cache/cord-266147-s8rxzm0t.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0887796306000940
doi: 10.1016/j.tmrv.2006.11.001
summary:
  Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as α1-protease inhibitor, von Willebrand factor, and protein C. A complete set of measures-and, most particularly, the use of dedicated viral inactivation and removal treatments-has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In the last few years, the complexity of the fractionation process has increased by (a) the introduction of chromatography to isolate new proteins from existing fractions such as cryoprecipitate, cryo-poor plasma, and Cohn fractions; (b) the integration of chromatography to the ethanol fractionation process to increase IgG recovery; and (c) the implementation of dedicated viral inactivation or removal steps.

abstract:
  Protein products fractionated from human plasma are an essential class of therapeutics used, often as the only available option, in the prevention, management, and treatment of life-threatening conditions resulting from trauma, congenital deficiencies, immunologic disorders, or infections. Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as α1-protease inhibitor, von Willebrand factor, and protein C. Because of the human origin of the starting material and the pooling of 10 000 to 50 000 donations required for industrial processing, the major risk associated to plasma products is the transmission of blood-borne infectious agents. A complete set of measures—and, most particularly, the use of dedicated viral inactivation and removal treatments—has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In this review, we summarize the practices of the modern plasma fractionation industry from the collection of the raw plasma material to the industrial manufacture of fractionated products. We describe the quality requirements of plasma for fractionation and the various treatments applied for the inactivation and removal of blood-borne infectious agents and provide examples of methods used for the purification of the various classes of plasma protein therapies. We also highlight aspects of the good manufacturing practices and the regulatory environment that govern the whole chain of production. In a regulated and professional environment, fractionated plasma products manufactured by modern processes are certainly among the lowest-risk therapeutic biological products in use today.


id: cord-267326-355q6k6k
title: Geospatial distribution of viromes in tropical freshwater ecosystems
author: Gu, Xiaoqiong
date: 2018-06-15
txt: ./txt/cord-267326-355q6k6k.txt
cache: ./cache/cord-267326-355q6k6k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29550725/
doi: 10.1016/j.watres.2018.03.017
summary:
  This study shows that spatial factors (e.g., reservoirs/tributaries, land use) are the main drivers of the viral community structure in tropical freshwater ecosystems. However, up till now, studies of land use impacts on the virome community in freshwater ecosystems are still limited as they mainly rely on traditional methodology (culture-based method or qPCR/RT-qPCR), which focuses on limited human virus targets without considering the whole picture of the viral community in the water environment (Corsi et al., 2014; Lenaker et al., 2017) . Thus, the objectives of this study were to: 1) investigate the overall virome distribution and diversity in diverse freshwater ecosystems (reservoirs/tributaries) in a tropical environment, 2) compare the virome community based on the different land use patterns, 3) assess the extent of human-related pathogenic viruses in surface waters, especially emerging zoonotic and human-related viruses, which may have been undetected before.

abstract:
  This study seeks to understand the general distribution of virome abundance and diversity in tropical freshwater ecosystems in Singapore and the geospatial distribution of the virome under different landuse patterns. Correlations between diversity, environmental parameters and land use patterns were analyzed and significant correlations were highlighted. Overall, the majority (65.5%) of the annotated virome belonged to bacteriophages. The percentage of Caudovirales was higher in reservoirs whereas the percentages of Dicistroviridae, Microviridae and Circoviridae were higher in tributaries. Reservoirs showed a higher Shannon-index virome diversity compared to upstream tributaries. Land use (urbanized, agriculture and parkland areas) influenced the characteristics of the virome distribution pattern. Dicistroviridae and Microviridae were enriched in urbanized tributaries while Mimiviridae, Phycodnaviridae, Siphoviridae and Podoviridae were enriched in parkland reservoirs. Several sequences closely related to the emerging zoonotic virus, cyclovirus, and the human-related virus (human picobirnavirus), were also detected. In addition, the relative abundance of PMMoV (pepper mild mottle virus) sequences was significantly correlated with RT-qPCR measurements (0.588 < r < 0.879, p < 0.05). This study shows that spatial factors (e.g., reservoirs/tributaries, land use) are the main drivers of the viral community structure in tropical freshwater ecosystems.


id: cord-269194-b1wlr3t7
title: Chapter 5 Clinical Applications of Quantitative Real-Time PCR in Virology
author: Engstrom-Melnyk, Julia
date: 2015-12-31
txt: ./txt/cord-269194-b1wlr3t7.txt
cache: ./cache/cord-269194-b1wlr3t7.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0580951715000069
doi: 10.1016/bs.mim.2015.04.005
summary:
  Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats. With the development and administration of newer drugs that target specific biological processes of HIV, routine and clinical monitoring of viral loads using a real-time quantitative PCR assay continues to be critical to predict treatment failure and early emergence of drug resistance mutations, within a timeframe that would increase subsequent treatment success.

abstract:
  Abstract Since the invention of the polymerase chain reaction (PCR) and discovery of Taq polymerase, PCR has become a staple in both research and clinical molecular laboratories. As clinical and diagnostic needs have evolved over the last few decades, demanding greater levels of sensitivity and accuracy, so too has PCR performance. Through optimisation, the present-day uses of real-time PCR and quantitative real-time PCR are enumerable. The technique, combined with adoption of automated processes and reduced sample volume requirements, makes it an ideal method in a broad range of clinical applications, especially in virology. Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. All of these serve vital roles in the continuum of care to enhance patient management. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats.


id: cord-270205-fw555w1u
title: Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors
author: Cillóniz, Catia
date: 2019-10-01
url: https://www.ncbi.nlm.nih.gov/pubmed/31115456/
doi: 10.1093/infdis/jiz257
abstract:
  We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis.


id: cord-270294-g95skuik
author: Johnstone, Jennie
date: 2008-12-31
txt: ./txt/cord-270294-g95skuik.txt
cache: ./cache/cord-270294-g95skuik.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1378/chest.08-0888
doi: 10.1378/chest.08-0888
summary:
  Furthermore, viral etiology studies in pneumonia are difficult to interpret as noninvasive viral detection methods are often considered to be only markers of infection rather than the cause of pneumonia." Clearly, much better knowledge of the potential role of respiratory viruses present in patients with pneumonia is needed. More recently, the introduction of highly sensitive nucleic acid amplification tests (NATs) has dramatically improved our ability to detect multiple viral pathogens such as influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza, and adenovirus. [13] [14] [15] To date, there have been few studies, 5, 7, [9] [10] [11] 16 ,17 reported in patients with pneumonia using NATs to detect viral infection, and these studies have either not included clinical data 7.9.11 or have not tested for all potentially important respiratory viruses in a comprehensive manner.lv-!?

title:
  Viral Infection in Adults Hospitalized With Community-Acquired Pneumonia Prevalence, Pathogens, and Presentation

abstract:
  Background The potential role of respiratory viruses in the natural history of community-acquired pneumonia (CAP) in adults has not been well described since the advent of nucleic amplification tests (NATs). Methods From 2004 to 2006, adults with CAP who were admitted to five hospitals were prospectively enrolled in the study, and clinical data, cultures, serology, and nasopharyngeal swabs were obtained. NATs from swabs were tested for influenza, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus 1–4, coronaviruses (OC43, 229E, and NL63), and adenovirus. Results A total of 193 patients were included; the median age was 71 years, 51% of patients were male, and 47% of patients had severe CAP. Overall, 75 patients (39%) had a pathogen identified. Of these pathogens, 29 were viruses (15%), 38 were bacteria (20%), 8 were mixed (4%), and the rest were “unknown.” Influenza (n = 7), hMPV (n = 7), and RSV (n = 5) accounted for most viral infections; other infections included rhinovirus (n = 4), parainfluenza (n = 3), coronavirus (n = 4), and adenovirus (n = 2). Streptococcus pneumoniae was the most common bacterial infection (37%). Compared with bacterial infection, patients with viral infection were older (76 vs 64 years, respectively; p = 0.01), were more likely to have cardiac disease (66% vs 32%, respectively; p = 0.006), and were more frail (eg, 48% with limited ambulation vs 21% of bacterial infections; p = 0.02). There were few clinically meaningful differences in presentation and no differences in outcomes according to the presence or absence of viral infection. Conclusions Viral infections are common in adults with pneumonia. Easily transmissible viruses such as influenza, hMPV, and RSV were the most common, raising concerns about infection control. Routine testing for respiratory viruses may be warranted for adults who have been hospitalized with pneumonia.


id: cord-270670-cubh9jxc
title: Viruses as Quasispecies: Biological Implications
author: Domingo, E.
date: 2006
txt: ./txt/cord-270670-cubh9jxc.txt
cache: ./cache/cord-270670-cubh9jxc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16568896/
doi: 10.1007/3-540-26397-7_3
summary:
  a Upon infection with an RNA virus (even with a single particle, as depicted here, enlarged about 10 6 times), viral replication leads to a mutant spectrum of related genomes, termed viral quasispecies. As further discussed in the text, in real infections multiple mutant spectra that can amount to a large number of replicating (or potentially replicating) genomes (up to 10 9 or even 10 12 per infected individual) provide highly dynamic mutant repertoire viral yields in cell culture, have been immensely powerful in characterizing the population dynamics of RNA viruses (see references in the reviews by Domingo and Holland 1997; Quiñones-Mateu and Arts 2002; Novella 2003; and the chapters by Quiñones-Mateu and Arts and Escarmís et al., this volume) . Despite these limitations, determination of nucleotide sequence heterogeneities in virus populations using correct reagents and adequate controls has consistently documented that most RNA viruses (and also some DNA viruses) consist of complex mutant spectra, with an average number of 1-100 mutations per genome (Sect.

abstract:
  During viral infections, the complex and dynamic distributions of variants, termed viral quasispecies, play a key role in the adaptability of viruses to changing environments and the fate of the population as a whole. Mutant spectra are continuously and avoidably generated during RNA genome replication, and they are not just a by-product of error-prone replication, devoid of biological relevance. On the contrary, current evidence indicates that mutant spectra contribute to viral pathogenesis, can modulate the expression of phenotypic traits by subpopulations of viruses, can include memory genomes that reflect the past evolutionary history of the viral lineage, and, furthermore, can participate in viral extinction through lethal mutagenesis. Also, mutant spectra are the target on which selection and random drift act to shape the long-term evolution of viruses. The biological relevance of mutant spectra is the central topic of this chapter.


id: cord-271495-5906wju4
author: Beldomenico, Pablo M.
date: 2020-05-11
url: https://www.ncbi.nlm.nih.gov/pubmed/32422375/
doi: 10.1016/j.ijid.2020.05.025
title:
  Do superspreaders generate new superspreaders? a hypothesis to explain the propagation pattern of COVID-19

abstract:
  Abstract The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries, and exponential propagation in others, in which the time that took to begin this explosive spread varies greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in infections of high intensity, which exposes new cases to high viral loads, and so on. This notion is supported by experimental veterinary research.


id: cord-272655-qeojdpez
title: Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia
author: Remolina, Yuly Andrea
date: 2015-11-17
url: https://doi.org/10.1371/journal.pone.0143152
doi: 10.1371/journal.pone.0143152
abstract:
  OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. SETTING: Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. PARTICIPANTS: Ninety-one adult patients with acute respiratory infection (55% were female). MEASUREMENTS: Viral identification, intensive care unit admission, hospital stay, and mortality. RESULTS: Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. CONCLUSIONS: The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality.


id: cord-273019-hbpfz8rt
title: Organelle dynamics and viral infections: at cross roads
author: Glingston, R. Sahaya
date: 2018-06-25
url: https://api.elsevier.com/content/article/pii/S1286457918301412
doi: 10.1016/j.micinf.2018.06.002
abstract:
  Viruses are obligate intracellular parasites of the host cells. A commonly accepted view is the requirement of internal membranous structures for various aspects of viral life cycle. Organelles enable favourable intracellular environment for several viruses. However, studies reporting organelle dynamics upon viral infections are scant. In this review, we aim to summarize and highlight modulations caused to various organelles upon viral infection or expression of its proteins.


id: cord-274080-884x48on
title: In vitro methods for testing antiviral drugs
author: Rumlová, Michaela
date: 2018-06-30
txt: ./txt/cord-274080-884x48on.txt
cache: ./cache/cord-274080-884x48on.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29292156/
doi: 10.1016/j.biotechadv.2017.12.016
summary:
  For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity.

abstract:
  Abstract Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses.


id: cord-274680-6pui91uu
title: Proinflammatory cytokines are associated with prolonged viral RNA shedding in COVID-19 patients
author: Gao, Chun
date: 2020-10-14
url: https://api.elsevier.com/content/article/pii/S1521661620307713
doi: 10.1016/j.clim.2020.108611
abstract:
  Since December 2019, Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic. We aimed to investigate the clinical characteristics and analyzed the risk factors for prolonged viral RNA shedding. We retrospectively collected data from 112 hospitalized COVID-19 patients in a single center in Wuhan, China. Factors associated with prolonged viral RNA shedding (≥28 days) were investigated. Forty-nine (43.8%) patients had prolonged viral RNA shedding. Patients with prolonged viral shedding were older and had a higher rate of hypertension. Proinflammatory cytokines, including interleukin-2R (IL-2R) and tumor necrosis factor-α (TNF-α), were significantly elevated in patients with prolonged viral shedding. Multivariate analysis revealed that hypertension, older age, lymphopenia and elevated serum IL-2R were independent risk factors for prolonged viral shedding. This comprehensive investigation revealed the distinct characteristics between patients with or without prolonged viral RNA shedding. Hypertension, older age, lymphopenia and high levels of proinflammatory cytokines may be correlated with prolonged viral shedding.


id: cord-274749-ji91qq9q
author: Lagare, Adamou
date: 2015-11-14
txt: ./txt/cord-274749-ji91qq9q.txt
cache: ./cache/cord-274749-ji91qq9q.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12879-015-1251-y
doi: 10.1186/s12879-015-1251-y
summary:
  The viruses most frequently detected in children with ARIs include respiratory syncytial virus (RSV), influenza virus (INF) types A and B, adenovirus (AV), parainfluenza virus (PIV), human metapneumovirus (HMPV) and rhinovirus (RV) [3] [4] [5] ; however, the clinical presentations of respiratory tract infections are similar, making it difficult to distinguish between etiologic agents without a laboratory diagnosis [6] . We aimed to document the prevalence of selected viral and bacterial infections among children <5 years of age hospitalized with severe acute respiratory illness (SARI) at selected hospitals in Niger from January 2010 through December 2012. We report the detection rate of selected viral and bacterial pathogens among children <5 years of age hospitalized with SARI in Niger. This study reports the detection rate of viral and bacterial pathogens among children <5 years of age hospitalized with SARI in Niger.

title:
  Viral and bacterial etiology of severe acute respiratory illness among children < 5 years of age without influenza in Niger

abstract:
  BACKGROUND: Globally, pneumonia is the leading cause of morbidity and mortality in children, with the highest burden experienced in sub-Saharan Africa and Asia. However, there is a dearth of information on the etiology of severe acute respiratory illness (SARI) in Africa, including Niger. METHODS: We implemented a retrospective study as part of national influenza sentinel surveillance in Niger. We randomly selected a sample of nasopharyngeal specimens collected from children <5 years of age hospitalized with SARI from January 2010 through December 2012 in Niger. The samples were selected from individuals that tested negative by real-time reverse transcription polymerase chain reaction (rRT-PCR) for influenza A and B virus. The samples were analyzed using the Fast Track Diagnostic Respiratory Pathogens 21plus Kit (BioMérieux, Luxemburg), which detects 23 respiratory pathogens including 18 viral and 5 bacterial agents. RESULTS: Among the 160 samples tested, 138 (86 %) tested positive for at least one viral or bacterial pathogen; in 22 (16 %) sample, only one pathogen was detected. We detected at least one respiratory virus in 126 (78 %) samples and at least one bacterium in 102 (64 %) samples. Respiratory syncytial virus (56/160; 35 %), rhinovirus (47/160; 29 %) and parainfluenza virus (39/160; 24 %) were the most common viral pathogens detected. Among bacterial pathogens, Streptococcus pneumoniae (90/160; 56 %) and Haemophilus influenzae type b (20/160; 12 %) predominated. CONCLUSIONS: The high prevalence of certain viral and bacterial pathogens among children <5 years of age with SARI highlights the need for continued and expanded surveillance in Niger.


id: cord-274780-fmnro0kw
title: Detection of astroviruses in feces of a cat with diarrhea
author: Hoshino, Y.
date: 1981
url: https://www.ncbi.nlm.nih.gov/pubmed/6798953/
doi: 10.1007/bf01320252
abstract:
  Astroviruses were detected by electron microscopy in the feces from a 4 month old kitten with diarrhea. The mean diameter of the viral particles was 28.7 nm, and they showed characteristic five- or six-pointed star-shaped surface configurations. The clinical disease manifested by the cat and the observed morphology of the viral particles are consistent with previous reports on astroviruses of other species.


id: cord-275683-1qj9ri18
title: Metagenomics in Virology
author: Roux, Simon
date: 2019-06-12
url: https://api.elsevier.com/content/article/pii/B9780128096338209576
doi: 10.1016/b978-0-12-809633-8.20957-6
abstract:
  Metagenomics, i.e., the sequencing and analysis of genomic information extracted directly from clinical or environmental samples, has become a fundamental tool to explore the viral world. Against the background of an extensive viral diversity revealed by metagenomics across many environments, new sequence assembly approaches that reconstruct complete genome sequences from metagenomes have recently revealed surprisingly cosmopolitan viruses in specific ecological niches. Metagenomics is also applied to clinical samples as a non-targeted diagnostic and surveillance tool. By enabling the study of these uncultivated viruses, metagenomics provides invaluable insights into the virus-host interactions, epidemiology, ecology, and evolution of viruses across all ecosystems.


id: cord-276908-9jthjf24
author: Gupta, Akanksha
date: 2020-07-06
url: https://www.ncbi.nlm.nih.gov/pubmed/32835089/
doi: 10.1002/slct.202001709
title:
  COVID‐19: Emergence of Infectious Diseases, Nanotechnology Aspects, Challenges, and Future Perspectives

abstract:
  Wuhan, a city of China, is the epicenter for the pandemic outbreak of coronavirus disease‐2019 (COVID‐19). It has become a severe public health challenge to the world and established a public health emergency of international worry. This infectious disease has pulled down the economy of almost all top developed nations. The coronaviruses (CoVs) known for various epidemics caused time to time. Infectious diseases such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), followed by COVID‐19, are all coronaviruses led outbreaks that scourged the history of mankind. CoVs evolved themselves to more infectious, transmissible, and more pandemic with time. To prevent the spread of the SARS‐CoV‐2, many countries have ordered the complete lockdown to combat the outbreak. This paper briefly discussed the historical background of CoVs and the evolution of human coronaviruses (HCoVs), the case studies and the development of their antiviral medications. The viral infection encountered with present‐day challenges and futuristic approaches with the help of nanotechnology to minimize the spread of infectious viruses. The antiviral drugs and their clinical advances, along with herbal medicines for viral inhibition and immunity boosters, are described. Elaboration of tables related to CoVs for the compilation of the literature has been adopted for the better understanding.


id: cord-279716-kxfc4npg
title: Bioaerosol sampling for the detection of aerosolized influenza virus
author: Blachere, Francoise M.
date: 2007-10-22
txt: ./txt/cord-279716-kxfc4npg.txt
cache: ./cache/cord-279716-kxfc4npg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19453416/
doi: 10.1111/j.1750-2659.2007.00020.x
summary:
  Background Influenza virus was used to characterize the efficacy of a cyclone‐based, two‐stage personal bioaerosol sampler for the collection and size fractionation of aerosolized viral particles. Results Based on qPCR results, we demonstrate that aerosolized viral particles were efficiently collected and separated according to aerodynamic size using the two‐stage bioaerosol sampler. In order to quantify the relative amount of viral particles or fungal spores collected at each stage of the bioaerosol sampler, qPCR was performed in parallel using either serial 10-fold dilutions of cDNA generated from a single dose of non-aerosolized FluMist Ò containing approximately 10 7 TCID 50 per influenza strain or genomic DNA isolated from 10 7 spores. In this study, by aerosolizing FluMist Ò , we demonstrate the recovery of aerosolized viral particles using the bioaerosol sampler and detection of influenza by qPCR.

abstract:
  Background Influenza virus was used to characterize the efficacy of a cyclone‐based, two‐stage personal bioaerosol sampler for the collection and size fractionation of aerosolized viral particles. Methods A Collison single‐jet nebulizer was used to aerosolize the attenuated FluMist® vaccine into a calm‐air settling chamber. Viral particles were captured with bioaerosol samplers that utilize 2 microcentrifuge tubes to collect airborne particulates. The first tube (T1) collects particles greater than 1.8 μm in diameter, while the second tube (T2) collects particles between 1.0 and 1.8 μm, and the back‐up filter (F) collects submicron particles. Following aerosolization, quantitative PCR was used to detect and quantify H1N1 and H3N2 influenza strains. Results Based on qPCR results, we demonstrate that aerosolized viral particles were efficiently collected and separated according to aerodynamic size using the two‐stage bioaerosol sampler. Most viral particles were collected in T2 (1‐1.8 μm) and on the back‐up filter (< 1 μm) of the bioaerosol sampler. Furthermore, we found that the detection of viral particles with the two‐stage sampler was directly proportional to the collection time. Consequently, viral particle counts were significantly greater at 40 minutes in comparison to 5, 10 and 20 minute aerosol collection points. Conclusions Due to a lack of empirical data, aerosol transmission of influenza is often questioned. Using FluMist®, we demonstrated that a newly developed bioaerosol sampler is able to recover and size fractionate aerosolized viral particles. This sampler should be an important tool for studying viral transmission in clinical settings and may significantly contribute towards understanding the modes of influenza virus transmission.


id: cord-280048-b4dz1lnn
title: Viral quasispecies
author: Domingo, Esteban
date: 2019-10-17
txt: ./txt/cord-280048-b4dz1lnn.txt
cache: ./cache/cord-280048-b4dz1lnn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31622336/
doi: 10.1371/journal.pgen.1008271
summary:
  Research on quasispecies has proceeded through several theoretical and experimental avenues that include continuing studies on evolutionary optimization and the origin of life, RNA-RNA interactions and replicator networks, the error threshold in variable fitness landscapes, consideration of chemical mutagenesis and proofreading mechanisms, evolution of tumor cells, bacterial populations or stem cells, chromosomal instability, drug resistance, and conformation distributions in prions (a class of proteins with conformation-dependent pathogenic potential; in this case the quasispecies is defined by a distribution of conformations) [16, 20] . Adaptability of RNA viruses is linked to parameters that facilitate exploration of sequence space: genome size (1.8 to 33 Kb), population size (variable but that can attain an impressive 10 12 individual genomes in an infected host at a given time), replication rate, mutation rate, fecundity (yield of viral particles per cell), and number of mutations required for a phenotypic change (surprisingly low for several relevant traits) (see [49] ).

abstract:
  Viral quasispecies refers to a population structure that consists of extremely large numbers of variant genomes, termed mutant spectra, mutant swarms or mutant clouds. Fueled by high mutation rates, mutants arise continually, and they change in relative frequency as viral replication proceeds. The term quasispecies was adopted from a theory of the origin of life in which primitive replicons) consisted of mutant distributions, as found experimentally with present day RNA viruses. The theory provided a new definition of wild type, and a conceptual framework for the interpretation of the adaptive potential of RNA viruses that contrasted with classical studies based on consensus sequences. Standard clonal analyses and deep sequencing methodologies have confirmed the presence of myriads of mutant genomes in viral populations, and their participation in adaptive processes. The quasispecies concept applies to any biological entity, but its impact is more evident when the genome size is limited and the mutation rate is high. This is the case of the RNA viruses, ubiquitous in our biosphere, and that comprise many important pathogens. In virology, quasispecies are defined as complex distributions of closely related variant genomes subjected to genetic variation, competition and selection, and that may act as a unit of selection. Despite being an integral part of their replication, high mutation rates have an upper limit compatible with inheritable information. Crossing such a limit leads to RNA virus extinction, a transition that is the basis of an antiviral design termed lethal mutagenesis.


id: cord-281844-c0uhcatg
title: Exacerbation of asthma and airway infection: is the virus the villain?
author: Costa, Lusmaia D.C.
date: 2014-12-31
url: https://doi.org/10.1016/j.jped.2014.07.001
doi: 10.1016/j.jped.2014.07.001
abstract:
  Abstract Objective To review the available literature on the association between acute viral respiratory tract infection and the onset of asthma exacerbations, identifying the most prevalent viruses, detection methods, as well as preventive and therapeutic aspects. Sources A search was conducted in PubMed, Lilacs, and SciELO databases, between the years 2002 and 2013, using the following descriptors: asthma exacerbation, virus, child, and acute respiratory infection. Summary of the findings A total of 42 original articles addressing the identification of respiratory viruses during episodes of asthma exacerbation were selected, mostly cross-sectional studies. There was a wide variation in the methodology of the assessed studies, particularly in relation to the children's age and methods of collection and viral detection. The results indicate that, in up to 92.2% of exacerbations, a viral agent was potentially the main triggering factor, and human rhinovirus was the most frequently identified factor. The pattern of viral circulation may have been responsible for the seasonality of exacerbations. The association between viral infections and allergic inflammation appears to be crucial for the clinical and functional uncontrolled asthma, but few studies have evaluated other triggering factors in association with viral infection. Conclusions Respiratory viruses are present in the majority of asthmatic children during episodes of exacerbation. The involved physiopathological mechanisms are yet to be fully established, and the synergism between allergic inflammation and viral infection appears to determine uncontrolled disease. The role of other triggering and protective agents is yet to be clearly determined.


id: cord-281916-v6u5mr2i
author: Bonnin, Paul
date: 2016-08-09
url: https://doi.org/10.1186/s12879-016-1730-9
doi: 10.1186/s12879-016-1730-9
title:
  Study and interest of cellular load in respiratory samples for the optimization of molecular virological diagnosis in clinical practice

abstract:
  BACKGROUND: Respiratory viral diagnosis of upper respiratory tract infections has largely developed through multiplex molecular techniques. Although the sensitivity of different types of upper respiratory tract samples seems to be correlated to the number of sampled cells, this link remains largely unexplored. METHODS: Our study included 800 upper respiratory tract specimens of which 400 negative and 400 positive for viral detection in multiplex PCR. All samples were selected and matched for age in these 2 groups. For the positive group, samples were selected for the detected viral species. RESULTS: Among the factors influencing the cellularity were the type of sample (p < 0.0001); patient age (p < 0.001); viral positive or negative nature of the sample (p = 0.002); and, for the positive samples, the number of viral targets detected (0.004 < p < 0.049) and viral species. CONCLUSION: The cellular load of upper respiratory samples is multifactorial and occurs for many in the sensitivity of molecular detection. However it was not possible to determine a minimum cellularity threshold allowing molecular viral detection. The differences according to the type of virus remain to be studied on a larger scale.


id: cord-286137-4cbh3u3z
author: Honce, Rebekah
date: 2020-08-13
txt: ./txt/cord-286137-4cbh3u3z.txt
cache: ./cache/cord-286137-4cbh3u3z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32790755/
doi: 10.1371/journal.ppat.1008711
abstract: nan
summary:
  In mineral-and vitamin-deficient mice, genetic mutations arise in coxsackie B and influenza virus populations that promote virulence even in well-nourished hosts [36] [37] [38] [39] [40] . Experimental evolution of CA/09 virus through two models of murine obesity resulted in a viral population displaying increased virulence upon inoculation of a wild-type host. Interestingly, arbovirus-infected obese or protein-deficient mice showed higher morbidity but lower viral diversity, and both malnourished models transmitted virus less efficiently, highlighting that the effects of nutrition may vary based on the natural life cycles of viral families [42] . In our studies with influenza virus, we linked the emergence of a more diverse and virulent viral population with blunted interferon responses in obese hosts. Interferon treatment of obese mice restricted the emergence of a diverse quasispecies and attenuated the virulence of the resulting viral population, strengthening the claim that a robust innate immune response restricts subsequent infection severity, possibly through reduced viral replication and acquisition of a genetically diverse viral population [8, 20, 41] .

title:
  They are what you eat: Shaping of viral populations through nutrition and consequences for virulence


id: cord-286219-qcx5ehnh
title: The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection
author: Calistri, Arianna
date: 2014-05-06
url: https://doi.org/10.3390/cells3020386
doi: 10.3390/cells3020386
abstract:
  Through the combined action of ubiquitinating and deubiquitinating enzymes, conjugation of ubiquitin to a target protein acts as a reversible post-translational modification functionally similar to phosphorylation. Indeed, ubiquitination is more and more recognized as a central process for the fine regulation of many cellular pathways. Due to their nature as obligate intracellular parasites, viruses rely on the most conserved host cell machineries for their own replication. Thus, it is not surprising that members from almost every viral family are challenged by ubiquitin mediated mechanisms in different steps of their life cycle and have evolved in order to by-pass or exploit the cellular ubiquitin conjugating system to maximize their chance to establish a successful infection. In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells.


id: cord-286328-ap0wfjhq
title: Nasal cytokine responses to natural colds in asthmatic children
author: Lewis, Toby C.
date: 2012-11-26
txt: ./txt/cord-286328-ap0wfjhq.txt
cache: ./cache/cord-286328-ap0wfjhq.txt
extension: .txt
mime: text/plain
url: https://deepblue.lib.umich.edu/bitstream/2027.42/94448/1/cea12005.pdf
doi: 10.1111/cea.12005
summary:
  CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes. To further examine the innate immune response to viral infection in children with asthma, we measured nasal aspirate cytokine levels in 16 asthmatic children before and after upper respiratory tract infections. We also examined the effects of upper respiratory tract infection on mRNA levels of selected markers of viral infection, including IFNs. Finally, we evaluated a new method of virus detection using a single polymerase chain reaction-ligation detection reaction (PCR-LDR) multiplex assay. We performed home measurements of respiratory symptoms and collected nasal secretions (for detection of viral RNA by PCR and host biomarkers by PCR and ELISA) on 3 days during a week when children were healthy (not reporting upper respiratory tract infection or asthma symptoms), and again during a week when they experienced cold or flu-like symptoms.

abstract:
  BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well-understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally-occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured by multiplex immune assay. mRNA expression for selected markers of viral infection was measured by RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 “well” weeks; 22 self-assessed “sick” weeks). Viral infections were detected in three of the “well” weeks and 17 of the “sick” weeks (10 rhinovirus, 3 coronavirus, 2 influenza A, 2 influenza B, 2 respiratory syncytial virus, 1 parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3 and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5 and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I and IRF7 mRNA. CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes.


id: cord-286337-qk90xb3a
title: Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia
author: Hanada, Shigeo
date: 2018-11-16
txt: ./txt/cord-286337-qk90xb3a.txt
cache: ./cache/cord-286337-qk90xb3a.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2018.02640
doi: 10.3389/fimmu.2018.02640
summary:
  While the effects of these alterations on risk of secondary bacterial pneumonia have not been studied, potential mechanisms by which these changes might modulate susceptibility to secondary bacterial infections include alterations in the nature and magnitude of the immune response in the host (microbiome on host effects) and facilitating growth of pathogens in the absence of normal commensals (inter-microbial effects). Given the effects of viruses on enhancing bacterial adherence to the epithelium (86) (87) (88) , it is perhaps not surprising that multiple studies of human subjects as well as in animal models have shown that viral infections are associated with increased colonization by potentially pathogenic bacteria (known as "pathobionts"). Another study of patients with 2009 pandemic H1N1 influenza infection revealed that the predominant phyla of the upper respiratory tract (nasal and nasopharyngeal samples) in patients harboring pandemic H1N1 were Actinobacteria, Firmicutes, and Proteobacteria although normal controls were not included; however, the authors suggested that flu is associated with an expansion of Proteobacteria (109) which is generally less abundant in healthy hosts.

abstract:
  Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.


id: cord-286843-8qh1pblc
title: Impact of microbial Aetiology on mortality in severe community-acquired pneumonia
author: Quah, Jessica
date: 2018-09-04
url: https://www.ncbi.nlm.nih.gov/pubmed/30180811/
doi: 10.1186/s12879-018-3366-4
abstract:
  BACKGROUND: The impact of different classes of microbial pathogens on mortality in severe community-acquired pneumonia is not well elucidated. Previous studies have shown significant variation in the incidence of viral, bacterial and mixed infections, with conflicting risk associations for mortality. We aimed to determine the risk association of microbial aetiologies with hospital mortality in severe CAP, utilising a diagnostic strategy incorporating molecular testing. Our primary hypothesis was that respiratory viruses were important causative pathogens in severe CAP and was associated with increased mortality when present with bacterial pathogens in mixed viral-bacterial co-infections. METHODS: A retrospective cohort study from January 2014 to July 2015 was conducted in a tertiary hospital medical intensive care unit in eastern Singapore, which has a tropical climate. All patients diagnosed with severe community-acquired pneumonia were included. RESULTS: A total of 117 patients were in the study. Microbial pathogens were identified in 84 (71.8%) patients. Mixed viral-bacterial co-infections occurred in 18 (15.4%) of patients. Isolated viral infections were present in 32 patients (27.4%); isolated bacterial infections were detected in 34 patients (29.1%). Hospital mortality occurred in 16 (13.7%) patients. The most common bacteria isolated was Streptococcus pneumoniae and the most common virus isolated was Influenza A. Univariate and multivariate logistic regression showed that serum procalcitonin, APACHE II severity score and mixed viral-bacterial infection were associated with increased risk of hospital mortality. Mixed viral-bacterial co-infections were associated with an adjusted odds ratio of 13.99 (95% CI 1.30–151.05, p = 0.03) for hospital mortality. CONCLUSIONS: Respiratory viruses are common organisms isolated in severe community-acquired pneumonia. Mixed viral-bacterial infections may be associated with an increased risk of mortality.


id: cord-287459-k9x3z2h1
title: The Role of Lipid Metabolism in COVID-19 Virus Infection and as a Drug Target
author: Abu-Farha, Mohamed
date: 2020-05-17
url: https://doi.org/10.3390/ijms21103544
doi: 10.3390/ijms21103544
abstract:
  The current Coronavirus disease 2019 or COVID-19 pandemic has infected over two million people and resulted in the death of over one hundred thousand people at the time of writing this review. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though multiple vaccines and treatments are under development so far, the disease is only slowing down under extreme social distancing measures that are difficult to maintain. SARS-COV-2 is an enveloped virus that is surrounded by a lipid bilayer. Lipids are fundamental cell components that play various biological roles ranging from being a structural building block to a signaling molecule as well as a central energy store. The role lipids play in viral infection involves the fusion of the viral membrane to the host cell, viral replication, and viral endocytosis and exocytosis. Since lipids play a crucial function in the viral life cycle, we asked whether drugs targeting lipid metabolism, such as statins, can be utilized against SARS-CoV-2 and other viruses. In this review, we discuss the role of lipid metabolism in viral infection as well as the possibility of targeting lipid metabolism to interfere with the viral life cycle.


id: cord-287711-gw8mgg4m
title: Cellulose-based virus-retentive filters: a review
author: Junter, Guy-Alain
date: 2017-06-01
txt: ./txt/cord-287711-gw8mgg4m.txt
cache: ./cache/cord-287711-gw8mgg4m.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32214924/
doi: 10.1007/s11157-017-9434-1
summary:
  Data from spiking studies quantifying the viral filtration performance of cellulosic filters are detailed, i.e., first, the virus reduction capacity of regenerated cellulose hollow fiber filters in the manufacturing process of blood products and, second, the efficiency of virus recovery/concentration from water samples by the viradel (virus adsorption–elution) method using charge modified, electropositive cellulosic filters or conventional electronegative cellulose ester microfilters. Data from spiking studies quantifying the viral filtration performance of cellulosic filters are detailed, i.e., first, the virus reduction capacity of regenerated cellulose hollow fiber filters in the manufacturing process of blood products and, second, the efficiency of virus recovery/concentration from water samples by the viradel (virus adsorption-elution) method using charge modified, electropositive cellulosic filters or conventional electronegative cellulose ester microfilters.

abstract:
  Viral filtration is a critical step in the purification of biologics and in the monitoring of microbiological water quality. Viral filters are also essential protection elements against airborne viral particles. The present review first focuses on cellulose-based filter media currently used for size-exclusion and/or adsorptive filtration of viruses from biopharmaceutical and environmental water samples. Data from spiking studies quantifying the viral filtration performance of cellulosic filters are detailed, i.e., first, the virus reduction capacity of regenerated cellulose hollow fiber filters in the manufacturing process of blood products and, second, the efficiency of virus recovery/concentration from water samples by the viradel (virus adsorption–elution) method using charge modified, electropositive cellulosic filters or conventional electronegative cellulose ester microfilters. Viral analysis of field water samples by the viradel technique is also surveyed. This review then describes cellulose-based filter media used in individual protection equipment against airborne viral pathogens, presenting innovative filtration media with virucidal properties. Some pros and cons of cellulosic viral filters and perspectives for cellulose-based materials in viral filtration are underlined in the review.


id: cord-287758-da11ypiy
title: COVID-19 therapy: what weapons do we bring into battle?
author: Mônica Vitalino de Almeida, Sinara
date: 2020-09-10
txt: ./txt/cord-287758-da11ypiy.txt
cache: ./cache/cord-287758-da11ypiy.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.bmc.2020.115757
doi: 10.1016/j.bmc.2020.115757
summary:
  The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell.

abstract:
  Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.


id: cord-287770-oxfnt2n4
author: Caricati, C. P.
date: 2013-06-27
txt: ./txt/cord-287770-oxfnt2n4.txt
cache: ./cache/cord-287770-oxfnt2n4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23804299/
doi: 10.1002/btpr.1758
summary:
  title: Safety of snake antivenom immunoglobulins: Efficacy of viral inactivation in a complete downstream process In this article, we used a wide panel of viruses to assess viral removal/inactivation of our downstream process for Snake Antivenom Immunoglobulin (SAI). Among the steps analyzed in the process, phenol addition was the most effective one, followed by heat, caprylic acid, and pepsin. The main steps are cited in sequential order (a) ammonium sulfate precipitation of immunoglobulins, (b) pepsin digestion to obtain F(ab'')2 fragments, (c) caprylic acid precipitation of nonimmunoglobulin proteins, (d) heat treatment, (e) ammonium sulfate precipitation of F(ab'')2 fragments, (f) tangential filtration, (g) ion-exchange chromatography, (h) tangential filtration, and (i) phenol addition. 34 We found no reports using both viruses as models for viral inactivation concerning the described purification steps. 52, 55 Phenol inactivated both viruses, which indicates that it might also be an effective preservative for human-derived immunoglobulins, when it comes to viral safety.

title:
  Safety of snake antivenom immunoglobulins: Efficacy of viral inactivation in a complete downstream process

abstract:
  Viral safety remains a challenge when processing a plasma‐derived product. A variety of pathogens might be present in the starting material, which requires a downstream process capable of broad viral reduction. In this article, we used a wide panel of viruses to assess viral removal/inactivation of our downstream process for Snake Antivenom Immunoglobulin (SAI). First, we screened and excluded equine plasma that cross‐reacted with any model virus, a procedure not published before for antivenoms. In addition, we evaluated for the first time the virucidal capacity of phenol applied to SAI products. Among the steps analyzed in the process, phenol addition was the most effective one, followed by heat, caprylic acid, and pepsin. All viruses were fully inactivated only by phenol treatment; heat, the second most effective step, did not inactivate the rotavirus and the adenovirus used. We therefore present a SAI downstream method that is cost‐effective and eliminates viruses to the extent required by WHO for a safe product. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:972–979, 2013


id: cord-289093-si8btsab
author: Beard, Philippa M.
date: 2014-06-05
txt: ./txt/cord-289093-si8btsab.txt
cache: ./cache/cord-289093-si8btsab.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pone.0098431
doi: 10.1371/journal.pone.0098431
summary:
  To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. The methodology in the previously published VACV screens varied considerably; Mercer et al [32] measured the growth of a thymidine-kinase-deficient VACV (strain Western Reserve) after only 8 h of infection, thereby identifying cellular proteins involved in the initial stages of virus replication but excluding analysis of viral spread.

title:
  A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference

abstract:
  Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.


id: cord-291063-de7v4e5s
title: Silencing Viral MicroRNA as a Novel Antiviral Therapy?
author: Moens, Ugo
date: 2009-05-28
txt: ./txt/cord-291063-de7v4e5s.txt
cache: ./cache/cord-291063-de7v4e5s.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1155/2009/419539
doi: 10.1155/2009/419539
summary:
  The expressions of EBV-encoded miRNAs in clinical samples and computational analysis to predict putative targets were applied to unravel the biological functions of EBV miRNAs. These approaches showed that the miR-BARTs are abundantly expressed in latently infected epithelial cells, nasopharyngeal carcinomas, EBV-associated gastric carcinoma cell lines and tissues, Burkitt''s lymphomas latency type I, EBV positive primary effusion lymphomas, and diffuse large B-cell lymphomas, but at a significantly lower level in B cells. However, computational alignment of the potential HIV-1 miRNAs with specific human T-cell mRNAs identified potential cellular targets including genes encoding CD4, CD28 and interleukin-2, IL-3, and IL-12 [119] . The idea of targeting viral transcripts is not new, and RNA interference has been demonstrated to efficiently mediate inhibition of replication of human pathogenic viruses such as HIV-1, HCV, dengue virus, severe acute respiratory syndrome (SARS) coronavirus, poliovirus, human rhinovirus, influenza A virus, hepatitis D virus, HBV, HSV-1, HPV, JCV, EBV, and CMV in cell culture (reviewed in [12] ).

abstract:
  Viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. Some viruses may also survive by transforming the infected cell into an immortal tumour cell. MicroRNAs are small non-coding transcripts that function as posttranscriptional regulators of gene expression. Viruses encode miRNAs that regulate expression of both cellular and viral genes, and contribute to the pathogenic properties of viruses. Hence, neutralizing the action of viral miRNAs expression by complementary single-stranded oligonucleotides or so-called anti-miRNAs may represent a strategy to combat viral infections and viral-induced pathogenesis. This review describes the miRNAs encoded by human viruses, and discusses the possible therapeutic applications of anti-miRNAs against viral diseases.


id: cord-292335-al6v3b9x
author: Crotty, Matthew P.
date: 2015-11-18
url: https://doi.org/10.1186/s13054-015-1120-5
doi: 10.1186/s13054-015-1120-5
title:
  Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship

abstract:
  INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.


id: cord-292416-3hhi4wps
title: Investigating an Emerging Virus During a Sudden Pandemic Outbreak
author: Sarid, Ronit
date: 2020-07-31
txt: ./txt/cord-292416-3hhi4wps.txt
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url: https://doi.org/10.5041/rmmj.10414
doi: 10.5041/rmmj.10414
summary:
  Five years later, in 2020, when the World Health Organization declared the coronavirus disease 2019 (COVID-19)-caused by the newly emerging SARS-CoV-2 virus-to be a pandemic, this talk was widely acknowledged to be almost prophetic. 24, 25 All four reportedly mild pathogenic coronaviruses are associated with 10%-30% of cases of the common cold, 26 -28 yet they have the potential to cause severe lower respiratory tract infection in infants, in the elderly, and in patients with other underlying illness, 29 while hCoV-OC43, like SARS-CoV-2, has been associated with neurologic dysfunction as well. Development of animal models for SARS-CoV-2 infection is vital in providing comprehensive understanding of the pathogenic mechanisms involved but may also serve for screening anti-viral drugs and vaccines. Accordingly, transfusion of convalescent plasma is likely to be beneficial to SARS-CoV-2, 45 ,46 yet its effect on virus shedding and disease outcome must be evaluated when given to healthy individuals and patients at different stages and severity of the disease.

abstract:
  At the time of writing, in July 2020, the recently emerging SARS-CoV-2 pandemic has attracted major attention to viral diseases, in particular coronaviruses. In spite of alarming molecular evidence, documentation of interspecies transmission in livestock, and the emergence of two new and relatively virulent human coronaviruses within a 10-year period, many gaps remain in the study and understanding of this family of viruses. This paper provides an overview of our knowledge regarding the coronavirus family, while highlighting their key biological properties in the context of our overall understanding of viral diseases.


id: cord-293038-pjjvfdnq
title: The unique architecture of Bunyamwera virus factories around the Golgi complex
author: Fontana, Juan
date: 2008-06-10
txt: ./txt/cord-293038-pjjvfdnq.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18547336/
doi: 10.1111/j.1462-5822.2008.01184.x
summary:
  We propose that this new structure, unique among enveloped viruses, assembles in association with the most stable component of Golgi stacks, the actin‐containing matrix scaffold, connecting viral replication and morphogenesis inside viral factories. Modified membranes harbouring viral replication complexes (RCs) frequently integrate into a complex structure known as the ''viral factory'' where the cytoskeleton participates, cell organelles are recruited and the different steps of the virus life cycle are sequentially connected. We propose that this new multifunctional structure associates with the actin-containing matrix of the Golgi stacks providing a stable scaffold for viral replication and early morphogenesis. LtA and CyD had very little or no effect, respectively, on viral replication and assembly as determined by measurement of infectious viral particles released to the culture supernatants at 6 and 10 h p.i. Complete tubes, virus budding profiles and viral particles assembled in Golgi stacks of cells treated with LtA, as observed in thin sections of treated cells studied by EM (not shown).

abstract:
  Viral factories are novel structures built by viruses in infected cells. During their construction organelles are recruited and build a large scaffold for viral replication and morphogenesis. We have studied how a bunyavirus uses the Golgi to build the factory. With the help of confocal and 3D ultrastructural imaging together with molecular mapping in situ and in vitro we have characterized a tubular structure that harbours the viral replication complexes in a globular domain. Numerous ribonucleoproteins were released from purified tubes disrupted in vitro. Actin and myosin I were identified by peptide mass fingerprinting in isolated tubes while actin and the viral NSm non‐structural protein were detected in the tubes' internal proteinaceous scaffold by immunogold labelling. Studies with NSm deletion mutants and drugs affecting actin showed that both NSm and actin are key factors for tube and virus assembly in Golgi. Three‐dimensional reconstructions based on oriented serial sections of infected cells showed that tubes anchor cell organelles to Golgi stacks and make contacts with intracellular viruses. We propose that this new structure, unique among enveloped viruses, assembles in association with the most stable component of Golgi stacks, the actin‐containing matrix scaffold, connecting viral replication and morphogenesis inside viral factories.


id: cord-294478-3ickafd3
title: Diagnostic Investigation of Emerging Viruses of Companion Animals
author: Kapil, Sanjay
date: 2008-05-22
url: https://www.ncbi.nlm.nih.gov/pubmed/18501276/
doi: 10.1016/j.cvsm.2008.02.009
abstract:
  In this article, the authors are specifically concerned with the timely and accurate detection of emerging diseases of small animals that are viral in origin. Veterinarians are bound to encounter emerging viruses in their practice. The problem is unavoidable, because viruses are highly mutagenic. Even the immune response dictates the nature of virus that evolves in a host. If the clinical signs and diagnostic methods fail to correlate, the veterinarian should work with the diagnostic laboratory to solve the diagnostic puzzle.


id: cord-294592-zwvr57a0
author: Mukherjee, Moumita
date: 2020-08-11
url: https://www.ncbi.nlm.nih.gov/pubmed/32780783/
doi: 10.1371/journal.pone.0237559
title:
  Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV-2

abstract:
  BACKGROUND: The world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV-2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5’ and 3’ untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon. METHODS: To have an idea of the global changes in 5’ and 3’-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV-2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by ‘RBPmap’ and ‘RNA22 v2’ respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue. RESULTS: We identified 28 unique variants in SARS-CoV-2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5’-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3’UTR among most of the continents. Furthermore, we found that despite the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs. CONCLUSION: Our results, shows for the first time in SARS-Cov-2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future.


id: cord-297960-4x1j0iqg
title: Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis
author: Bösl, Korbinian
date: 2019-10-04
txt: ./txt/cord-297960-4x1j0iqg.txt
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mime: text/plain
url: https://doi.org/10.3389/fimmu.2019.02186
doi: 10.3389/fimmu.2019.02186
summary:
  Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Global systems-level approaches including functional RNAi screens, interactome mapping technologies such as affinity-purification mass spectrometry (AP-MS), quantitative proteomics, and CRISPR/Cas9-based screens have provided unparalleled details and insights into the dynamics of host proteome in immune cells (21) (22) (23) (24) , host-virus interactome (15-17, 25, 26) , and also identified important host dependency factors of various viruses (25, 27, 28) . We hypothesized that combining a meta-analysis of host-virus protein-protein interactions of multiple viruses and functional RNAi screens would provide novel insights for developing broadspectrum antiviral strategies. High-Definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms

abstract:
  Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.


id: cord-298019-gf2asni1
title: gH625: A milestone in understanding the many roles of membranotropic peptides
author: Galdiero, Stefania
date: 2014-10-12
txt: ./txt/cord-298019-gf2asni1.txt
cache: ./cache/cord-298019-gf2asni1.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0005273614003411
doi: 10.1016/j.bbamem.2014.10.006
summary:
  While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. Peptides with a propensity for membrane binding can also interfere with enveloped virus entry by direct physical interaction with the hydrophobic surfaces present on cell membranes and/or fusion proteins. Since not all membranotropic peptides are able to cross the membrane bilayer, it is essential to identify structural characteristics of hydrophobic peptides know to enter the cell membrane to highlight any feature that is involved in the penetration which may help in the design of novel delivery tools. Dendrimer functionalization with a membrane-interacting domain of herpes simplex virus type 1: towards intracellular delivery

abstract:
  Here, we review the current knowledge about viral derived membranotropic peptides, and we discuss how they may be used for many therapeutic applications. While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. The peptide gH625 has been extensively used for all these purposes and provides a significant contribution to the field. We describe the roles of this sequence in order to close the gap between the many functions that are now emerging for membranotropic peptides.


id: cord-298033-kzdp9edn
title: Quasispecies dynamics in disease prevention and control
author: Domingo, Esteban
date: 2019-11-08
txt: ./txt/cord-298033-kzdp9edn.txt
cache: ./cache/cord-298033-kzdp9edn.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128163313000088
doi: 10.1016/b978-0-12-816331-3.00008-8
summary:
  Quasispecies dynamics in disease prevention and control following statement will be obvious to the reader: "If a single mutation is able to confer resistance to an antiviral agent, and the mutation does not cause a significant selective disadvantage to the virus (fitness decrease) in the considered environment, a drug-resistant virus mutant will be present in most, if not all, virus populations" (Domingo, 1989) . The phenotypic barrier to drug resistance is equivalent to the fitness cost inflicted upon the virus by the mutations and corresponding amino acid substitution(s) required for resistance [Fitness cost is treated in Chapter 4 (Section 4.6) and in Chapter 7 (Section 7.4.2) in connection with the frequency of monoclonal antibody-or cytotoxic T-cell-escape mutants in viral populations]. For viruses that replicate in cell culture, it is possible to estimate the minimal viral population size needed to select a drug-resistant mutant which is generally positively correlated with the genetic barrier ( Fig. 8.5 ).

abstract:
  Medical interventions to prevent and treat viral disease constitute evolutionary forces that may modify the genetic composition of viral populations that replicate in an infected host and influence the genomic composition of those viruses that are transmitted and progress at the epidemiological level. Given the adaptive potential of viruses in general and the RNA viruses in particular, the selection of viral mutants that display some degree of resistance to inhibitors or vaccines is a tangible challenge. Mutant selection may jeopardize control of the viral disease. Strategies intended to minimize vaccination and treatment failures are proposed and justified based on fundamental features of viral dynamics explained in the preceding chapters. The recommended use of complex, multiepitopic vaccines, and combination therapies as early as possible after initiation of infection falls under the general concept that complexity cannot be combated with simplicity. It also follows that sociopolitical action to interrupt virus replication and spread as soon as possible is as important as scientifically sound treatment designs to control viral disease on a global scale.


id: cord-302111-kg0dmgq0
author: Darden, Dijoia B.
date: 2020-04-29
txt: ./txt/cord-302111-kg0dmgq0.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32426751/
doi: 10.1097/cce.0000000000000109
summary:
  Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Key Words: coronavirus; immunology; influenza virus; severe acute respiratory syndrome; viral pneumonia P neumonia is the leading infectious cause of hospitalization among adults and children in the United States (1) . Given the rapid spread of this virus and its association with severe pulmonary disease, the purpose of this review is to provide an overview of the presentation and immunology of viral pneumonia, principles of early management, and application to COVID-19.

title:
  The Clinical Presentation and Immunology of Viral Pneumonia and Implications for Management of Coronavirus Disease 2019

abstract:
  This review will briefly examine the clinical presentation and important immunology of viral pneumonia with a focus on severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: The most relevant, original and review literature were assessed for inclusion in this review. Sources included the Centers for Disease Control and Prevention, World Health Organization, and PubMed. CONCLUSIONS: Pneumonia is a leading cause of hospitalization and death worldwide, with viral etiologies being very common. Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Symptoms of viral pneumonia include common respiratory tract infection symptoms of cough, fever, and shortness of breath. Immunologic changes include up-regulation of airway pro-inflammatory cytokines and pathogen- and damage-associated molecular patterns contributing to cytokine and genomic changes. Coronavirus disease 2019 clinical presentation is typical of viral pneumonia with an increased prevalence of early pulmonary infiltrates and lymphopenia. Principles of early coronavirus disease 2019 management and isolation as well as potential therapeutic approaches to the emerging pandemic are discussed.


id: cord-303330-zh8wzza5
author: Magleby, Reed
date: 2020-06-30
url: https://doi.org/10.1093/cid/ciaa851
doi: 10.1093/cid/ciaa851
title:
  Impact of SARS-CoV-2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients with Coronavirus Disease 2019

abstract:
  BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates, but the impact of viral burden on these outcomes is unknown. METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 from March 30 to April 30, 2020 at two hospitals in New York City. SARS-CoV-2 viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared patient characteristics and outcomes among patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with risk of intubation and in-hospital mortality. RESULTS: We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% with a high viral load (Ct<25; n=220), 17.6% with a medium viral load (Ct 25-30; n=216), and 6.2% with a low viral load (Ct>30; n=242; P<0.001). The risk of intubation was also higher in patients with a high viral load (29.1%), compared to those with a medium (20.8%) or low viral load (14.9%; P<0.001). High viral load was independently associated with mortality (adjusted odds ratio [aOR] 6.05; 95% confidence interval [CI]: 2.92-12.52; P<0.001) and intubation (aOR 2.73; 95% CI: 1.68-4.44; P<0.001) in multivariate models. CONCLUSIONS: Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.


id: cord-304424-048xo7jn
title: A decade of RNA virus metagenomics is (not) enough
author: Greninger, Alexander L.
date: 2018-01-15
txt: ./txt/cord-304424-048xo7jn.txt
cache: ./cache/cord-304424-048xo7jn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29055712/
doi: 10.1016/j.virusres.2017.10.014
summary:
  That same year 36,789 colony sequences from DNase-treated RNA extracted from viral concentrates of human feces revealed a preponderance of pepper mild mottle virus and other plant viruses, but no new human viruses (Zhang et al., 2005) . While finding a new virus in the environment is not necessarily a problem in either DNA or RNA, the low fidelity of RNA polymerases and the sequence space they are capable of sampling, along with the possibility of recombination, lend themselves to new species and genera that are the trophies of metagenomic viral discovery. While metagenomics delivered on the promise of finding novel human viruses, viral discovery in humans has increasingly become a tragic story of patients interacting with the wrong squirrel or tick on the wrong day and most samples sequenced are frankly negative (Hoffmann et al., 2015; McMullan et al., 2012) . The greatest paradigm shifter in recent viral metagenomics work has been the sheer number and diversity of novel RNA viruses present in arthropods and invertebrates.

abstract:
  It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found.


id: cord-305195-e41yfo89
title: Viral Epidemiology: Tracking Viruses with Smartphones and Social Media
author: Rainwater-Lovett, Kaitlin
date: 2016-02-12
url: https://api.elsevier.com/content/article/pii/B9780128009642000185
doi: 10.1016/b978-0-12-800964-2.00018-5
abstract:
  The science of epidemiology has been developed over the last 200 years, using traditional methods to describe the distribution of diseases by person, place, and time. However, in the last several decades, a new set of technologies has become available, based on the methods of computer sciences, systems biology, and the extraordinary powers of the Internet. Technological and analytical advances can enhance traditional epidemiological methods to study the emergence, epidemiology, and transmission dynamics of viruses and associated diseases. Social media are increasingly used to detect the emergence and geographic spread of viral disease outbreaks. Large-scale population movement can be estimated using satellite imagery and mobile phone use, and fine-scale population movement can be tracked using global positioning system loggers, allowing estimation of transmission pathways and contact patterns at different spatial scales. Advances in genomic sequencing and bioinformatics permit more accurate determination of viral evolution and the construction of transmission networks, also at different spatial and temporal scales. Phylodynamics links evolutionary and epidemiological processes to better understand viral transmission patterns. More complex and realistic mathematical models of virus transmission within human and animal populations, including detailed agent-based models, are increasingly used to predict transmission patterns and the impact of control interventions such as vaccination and quarantine. In this chapter, we will briefly review traditional epidemiological methods and then describe the new technologies with some examples of their application.


id: cord-306424-gf0bglm0
title: Interaction of the innate immune system with positive-strand RNA virus replication organelles
author: Scutigliani, Enzo Maxim
date: 2017-06-27
url: https://api.elsevier.com/content/article/pii/S1359610117300667
doi: 10.1016/j.cytogfr.2017.05.007
abstract:
  The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines. However, +RNA viruses developed various methods to avoid detection and downstream signaling, including isolation of viral RNA replication in membranous viral replication organelles (ROs). These structures therefore play a central role in infection, and consequently, loss of RO integrity might simultaneously result in impaired viral replication and enhanced antiviral signaling. This review summarizes the first indications that the innate immune system indeed has tools to disrupt viral ROs and other non- or aberrant-self membrane structures, and may do this by marking these membranes with proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC3) and ubiquitin, resulting in the recruitment of IFN-inducible GTPases. Further studies should evaluate whether this process forms a general effector mechanism in +RNA virus infection, thereby creating the opportunity for development of novel antiviral therapies.


id: cord-306921-3afgpunj
title: Recent advances on the role of host factors during non-poliovirus enteroviral infections
author: Owino, Collins Oduor
date: 2019-06-19
txt: ./txt/cord-306921-3afgpunj.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/31215493/
doi: 10.1186/s12929-019-0540-y
summary:
  A small siRNA screen targeting human membrane trafficking genes identified vasolin-containing protein (VCP-p97) as an important protein essential after PV viral replication and it interacts and colocalizes with 2 BC/2C as well as 3AB/3B in poliovirus infected cells [83] . Human host factors-viral protein studies identified nuclear factor; adenosine-uridine (AU)-rich element RNA binding factor 1 (AUF1) is targeted for cleavage by CV-B3 viral 3C protease upon translocation to the cytoplasm for enhanced stability of the IRES dependent viral RNA production [112] , similar antiviral observations were made for poliovirus, coxsackievirus and human rhinovirus [113] . A subsequent study by Mohamud and colleagues demonstrated that SQSTM1 and another host factor calcium binding and coiled-coil domain-containing protein 2/nuclear dot 10 protein 52 (CALCOCO2) regulate CV-B3 virus infection by targeting autophagy receptors; via their interaction with viral protein 1 [177] .

abstract:
  Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus. Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses. This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections.


id: cord-307354-dkwcheu0
title: Emerging roles for RNA degradation in viral replication and antiviral defense
author: Abernathy, Emma
date: 2015-05-31
txt: ./txt/cord-307354-dkwcheu0.txt
cache: ./cache/cord-307354-dkwcheu0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virol.2015.02.007
doi: 10.1016/j.virol.2015.02.007
summary:
  Alpha-herpesviruses such as herpes simplex-1 (HSV-1) express a FEN1-like nuclease termed virion host shutoff protein (vhs) that is directed to mRNAs through interactions with the translation Fig. 1 . Quality control decay pathways such as NMD recognize aberrant mRNAs during translation, including the presence of premature termination codons (PTC), and induce endonucleolytic cleavage, whereupon the fragments are degraded by exonucleases. The RNAi pathway restricts gene expression by processing the long double stranded RNAs frequently generated during viral replication into short interfering RNAs (siR-NAs), which guide endonucleolytic cleavage of complementary target mRNAs. Although mammalian cells possess the RNAi machinery, in most cases RNAi does not appear to play a significant antiviral role, and has instead been supplanted by the protein-based interferon response (Cullen, 2014) . Small interfering RNAs that deplete the cellular translation factor eIF4H impede mRNA degradation by the virion host shutoff protein of herpes simplex virus

abstract:
  Abstract Viral replication significantly alters the gene expression landscape of infected cells. Many of these changes are driven by viral manipulation of host transcription or translation machinery. Several mammalian viruses encode factors that broadly dampen gene expression by directly targeting messenger RNA (mRNA). Here, we highlight how these factors promote mRNA degradation to globally regulate both host and viral gene expression. Although these viral factors are not homologous and use distinct mechanisms to target mRNA, many of them display striking parallels in their strategies for executing RNA degradation and invoke key features of cellular RNA quality control pathways. In some cases, there is a lack of selectivity for degradation of host versus viral mRNA, indicating that the purposes of virus-induced mRNA degradation extend beyond redirecting cellular resources towards viral gene expression. In addition, several antiviral pathways use RNA degradation as a viral restriction mechanism, and we will summarize new findings related to how these host-encoded ribonucleases target and destroy viral RNA.


id: cord-307813-elom30nx
title: Advancements in Host-Based Interventions for Influenza Treatment
author: Yip, Tsz-Fung
date: 2018-07-10
url: https://doi.org/10.3389/fimmu.2018.01547
doi: 10.3389/fimmu.2018.01547
abstract:
  Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease.


id: cord-307817-2vy28i4m
title: Current progress in antiviral strategies
author: Lou, Zhiyong
date: 2014-01-14
url: https://www.sciencedirect.com/science/article/pii/S0165614713002265
doi: 10.1016/j.tips.2013.11.006
abstract:
  The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. Virus-targeting antivirals can function directly or indirectly to inhibit the biological functions of viral proteins, mostly enzymatic activities, or to block viral replication machinery. Host-targeting antivirals target the host proteins that are involved in the viral life cycle, regulating the function of the immune system or other cellular processes in host cells. Here we review key targets and considerations for the development of both antiviral strategies.


id: cord-308126-wpxhk0pf
title: Common Cold and Acute Rhinosinusitis: Up-to-Date Management in 2020
author: Jaume, Francesca
date: 2020-06-03
url: https://www.ncbi.nlm.nih.gov/pubmed/32495003/
doi: 10.1007/s11882-020-00917-5
abstract:
  PURPOSE OF REVIEW: The purposes of the review are as follows: (1) to define acute rhinosinusitis (ARS) and their phenotypes, (2) to highlight the ARS management according to international guidelines, (3) to compare the physicians’ management with the ARS guideline recommendations, and (4) to report ARS socioeconomic burden. RECENT FINDINGS: Bacterial and non-bacterial ARS have similar symptoms, although they can be discriminated by using a combination of specific signs and symptoms. The prescription of antibiotics should be limited to clearly suspected bacterial ARS. There is an overuse of diagnosis tools and treatment prescriptions. The total cost per ARS episode in Europe is over €1000. SUMMARY: ARS is mainly an inflammatory disease triggered by viral infection, and few cases end up developing bacterial infection. In most of the cases, it is a self-resolving disease which diagnosis is mainly clinical and the treatment symptomatic. The incidence of complications is low and independent of antibiotic use. There is a high socioeconomic burden associated to ARS.


id: cord-309642-wwaa6ls0
title: Pathogenesis of Viral Infections
author: Potgieter, Leon N.D.
date: 1986-11-30
txt: ./txt/cord-309642-wwaa6ls0.txt
cache: ./cache/cord-309642-wwaa6ls0.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0195561686501297
doi: 10.1016/s0195-5616(86)50129-7
summary:
  7 · 18 · 84 · 133 Such restrictions function at the cellular level either as the presence or absence of appropriate cell surface receptors (in some instances, they have been shown to be inherited as dominant alleles in a Mendelian manner) 9 · 18 · 26 · 46 · 68 · 97 ·u 9 · 120 or the intracellular hospitality of the cell (several genetic host restrictions on virus replication have been identified).18·32·59·80·82·108·109·120·126 Restricted growth of several DNA viruses in some cells results in transformation without production of progeny viruses. 112 The phenomenon appears to be mediated by virus-induced receptors on the surface membrane of cells and may be one mechanism of the often-encountered secondary bacterial infections associated with viral diseases. 51 · 52 · 104 Viral respiratory tract disease is a consequence of mechanical and biochemical injury to epithelial cells and alveolar macrophages, which can, in the most severe instances, result in secondary bacterial infection, pneumonia, and death.

abstract:
  The article considers factors that influence pathogenesis, initiation of infection, dissemination of virus within a host, lytic viral infections, viral immunosuppression, viral immunopathology, and viral oncogenesis.


id: cord-310920-itqwhi6a
title: Integrated Approaches to Reveal Mechanisms by which RNA Viruses Reprogram the Cellular Environment
author: Haddad, Christina
date: 2020-07-02
url: https://api.elsevier.com/content/article/pii/S1046202320301249
doi: 10.1016/j.ymeth.2020.06.013
abstract:
  RNA viruses are major threats to global society and mass outbreaks can cause long-lasting damage to international economies. RNA and related retro viruses represent a large and diverse family that contribute to the onset of human diseases such as AIDS; certain cancers like T cell lymphoma; severe acute respiratory illnesses as seen with COVID-19; and others. The hallmark of this viral family is the storage of genetic material in the form of RNA, and upon infecting host cells, their RNA genomes reprogram the cellular environment to favor productive viral replication. RNA is a multifunctional biomolecule that not only stores and transmits heritable information, but it also has the capacity to catalyze complex biochemical reactions. It is therefore no surprise that RNA viruses use this functional diversity to their advantage to sustain chronic or lifelong infections. Efforts to subvert RNA viruses therefore requires a deep understanding of the mechanisms by which these pathogens usurp cellular machinery. Here, we briefly summarize several experimental techniques that individually inform on key physicochemical features of viral RNA genomes and their interactions with proteins. Each of these techniques provide important vantage points to understand the complexities of virus-host interactions, but we attempt to make the case that by integrating these and similar methods, more vivid descriptions of how viruses reprogram the cellular environment emerges. These vivid descriptions should expedite the identification of novel therapeutic targets.


id: cord-312332-rwmuucsp
author: Dicker, Kate
date: 2020-09-10
url: https://www.ncbi.nlm.nih.gov/pubmed/32921578/
doi: 10.1016/j.semcdb.2020.08.002
title:
  The importance of virion-incorporated cellular RNA-Binding Proteins in viral particle assembly and infectivity

abstract:
  RNA is a central molecule in RNA virus biology due to its dual function as messenger and genome. However, the small number of proteins encoded by viral genomes is insufficient to enable virus infection. Hence, viruses hijack cellular RNA-binding proteins (RBPs) to aid replication and spread. In this review we discuss the ‘knowns’ and ‘unknowns’ regarding the contribution of host RBPs to the formation of viral particles and the initial steps of infection in the newly infected cell. Through comparison of the virion proteomes of ten different human RNA viruses, we confirm that a pool of cellular RBPs are typically incorporated into viral particles. We describe here illustrative examples supporting the important functions of these RBPs in viral particle formation and infectivity and we propose that the role of host RBPs in these steps can be broader than previously anticipated. Understanding how cellular RBPs regulate virus infection can lead to the discovery of novel therapeutic targets against viruses.


id: cord-314024-n6l2804j
title: Timing of antiviral treatment initiation is critical to reduce SARS-Cov-2 viral load
author: Gonçalves, Antonio
date: 2020-04-07
txt: ./txt/cord-314024-n6l2804j.txt
cache: ./cache/cord-314024-n6l2804j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32511641/
doi: 10.1101/2020.04.04.20047886
summary:
  We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer 39 viral growth parameters and predict the effects of antiviral treatments. We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer 39 viral growth parameters and predict the effects of antiviral treatments. We 162 considered a simple case where the drug effectiveness is assumed to be constant after therapy 163 initiation (see methods) and we calculated the minimal efficacy that would be needed to 164 generate more than 2 logs of viral decline at peak viral load in the 13 studied patients (Fig. 1) . For a putative 167 treatment initiated at the time of infection, symptom onset, or 3 days post symptom onset, a 168 median efficacy of at least 60, 90 and 99% in reducing viral replication would be needed, 169 respectively, to generate more than 2 log of decline in the peak viral load (Fig. 1) .

abstract:
  We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than 2 logs, drug efficacy needs to be greater than 80% if treatment is administered after symptom onset; an efficacy of 50% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 20-70% efficacy. They may help control virus if administered very early, but may not have a major effect in severe patients.


id: cord-314560-rswa5zdn
title: Interfering antiviral immunity: application, subversion, hope?
author: Manjunath, N.
date: 2006-06-06
txt: ./txt/cord-314560-rswa5zdn.txt
cache: ./cache/cord-314560-rswa5zdn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16753342/
doi: 10.1016/j.it.2006.05.006
summary:
  RNA interference (RNAi), initially recognized as a natural antiviral mechanism in plants, has rapidly emerged as an invaluable tool to suppress gene expression in a sequence-specific manner in all organisms, including mammals. However, in recent years, a new type of genomic immunity mediated by RNA interference (RNAi) has emerged and has sparked intense interest as a potential treatment strategy for a variety of diseases, including viral infections, cancer and degenerative diseases [1] [2] [3] [4] . In RNAi, long double-stranded (ds) RNA generated during viral infection is cleaved by an enzyme termed Dicer into short, 21-23 nucleotide (nt) dsRNA molecules termed small interfering (si)RNAs that mediate sequence-specific gene silencing [5, 6] . A landmark development in the field occurred with the discovery that the introduction of 21-nt-long synthetic RNA resembling the Dicer-processed siRNA into mammalian cells induces sequence-specific gene silencing without evoking the interferon response [10] .

abstract:
  RNA interference (RNAi), initially recognized as a natural antiviral mechanism in plants, has rapidly emerged as an invaluable tool to suppress gene expression in a sequence-specific manner in all organisms, including mammals. Its potential to inhibit the replication of a variety of viruses has been demonstrated in vitro and in vivo in mouse and monkey models. These results have generated profound interest in the use of this technology as a potential treatment strategy for viral infections for which vaccines and drugs are unavailable or inadequate. In this review, we discuss the progress made within the past 2–3 years towards harnessing the potential of RNAi for clinical application in viral infections and the hurdles that have yet to be overcome.


id: cord-317037-1qydcc5e
author: Kumar, Asit
date: 2020-08-13
url: https://doi.org/10.3390/v12080887
doi: 10.3390/v12080887
title:
  Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention

abstract:
  Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. They are released via a direct outward budding and fission of plasma membrane blebs into the extracellular space to either facilitate virus propagation or regulate the immune responses. Moreover, EVs generated by virus-infected cells can incorporate virulence factors including viral protein and viral genetic material, and thus can resemble noninfectious viruses. Interactions of EVs with recipient cells have been shown to activate signaling pathways that may contribute to a sustained cellular response towards viral infections. EVs, by utilizing a complex set of cargos, can play a regulatory role in viral infection, both by facilitating and suppressing the infection. EV-based antiviral and antiretroviral drug delivery approaches provide an opportunity for targeted drug delivery. In this review, we summarize the literature on EVs, their associated involvement in transmission in viral infections, and potential therapeutic implications.


id: cord-317277-rr9zue4l
title: Viral cell-to-cell spread: Conventional and non-conventional ways
author: Cifuentes-Munoz, Nicolas
date: 2020-09-29
txt: ./txt/cord-317277-rr9zue4l.txt
cache: ./cache/cord-317277-rr9zue4l.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0065352720300427
doi: 10.1016/bs.aivir.2020.09.002
summary:
  Cell-free viral particles can be released into the extracellular space through different mechanisms, such as: (a) cell lysis induced by viral proteins, as is the case for many non-enveloped viruses such as reoviruses, rotaviruses, adenoviruses and picornaviruses (Giorda and Hebert, 2013; Hu et al., 2012; Nieva et al., 2012) ; (b) by budding directly from the plasma membrane, where virions acquire their envelope, as is the case of human immunodeficiency virus (HIV-1), influenza, paramyxoviruses, and pneumoviruses (Lorizate and Krausslich, 2011; Votteler and Sundquist, 2013; Weissenhorn et al., 2013) ; (c) by exocytosis of intracellularly assembled viral particles, as is the case for bunyaviruses, flaviviruses and coronaviruses (Cifuentes-Munoz et al., 2014; Lorizate and Krausslich, 2011) . An interesting observation made for alphaviruses is that the filopodia-like extensions are not able to transfer cytosolic or plasma membrane components, suggesting they are not openended connections like TNTs. Instead, viral particles are hypothesized to bud into a protected space at the filopodial tip and then rapidly enter the target cell, preventing access of neutralizing antibodies.

abstract:
  A critical step in the life cycle of a virus is spread to a new target cell, which generally involves the release of new viral particles from the infected cell which can then initiate infection in the next target cell. While cell-free viral particles released into the extracellular environment are necessary for long distance spread, there are disadvantages to this mechanism. These include the presence of immune system components, the low success rate of infection by single particles, and the relative fragility of viral particles in the environment. Several mechanisms of direct cell-to-cell spread have been reported for animal viruses which would avoid the issues associated with cell-free particles. A number of viruses can utilize several different mechanisms of direct cell-to-cell spread, but our understanding of the differential usage by these pathogens is modest. Although the mechanisms of cell-to-cell spread differ among viruses, there is a common exploitation of key pathways and components of the cellular cytoskeleton. Remarkably, some of the viral mechanisms of cell-to-cell spread are surprisingly similar to those used by bacteria. Here we summarize the current knowledge of the conventional and non-conventional mechanisms of viral spread, the common methods used to detect viral spread, and the impact that these mechanisms can have on viral pathogenesis.


id: cord-318495-1w74wf02
title: Defective viral genomes are key drivers of the virus–host interaction
author: Vignuzzi, Marco
date: 2019-06-03
url: https://doi.org/10.1038/s41564-019-0465-y
doi: 10.1038/s41564-019-0465-y
abstract:
  Viruses survive often harsh host environments, yet we know little about the strategies they utilize to adapt and subsist given their limited genomic resources. We are beginning to appreciate the surprising versatility of viral genomes and how replication-competent and -defective virus variants can provide means for adaptation, immune escape and virus perpetuation. This Review summarizes current knowledge of the types of defective viral genomes generated during the replication of RNA viruses and the functions that they carry out. We highlight the universality and diversity of defective viral genomes during infections and discuss their predicted role in maintaining a fit virus population, their impact on human and animal health, and their potential to be harnessed as antiviral tools.


id: cord-318749-k91oku7h
title: Selective regulation in ribosome biogenesis and protein production for efficient viral translation
author: Dong, Hui-Jun
date: 2020-10-29
txt: ./txt/cord-318749-k91oku7h.txt
cache: ./cache/cord-318749-k91oku7h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33124672/
doi: 10.1007/s00203-020-02094-5
summary:
  Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Similarly, ribosomes are required for the protein synthesis of host cells and viruses, but the biogenesis factor RBFs can also impact the proliferation of virus and cell-intrinsic immune responses. The multifunctional nucleolar phosphoprotein nucleophosmin (NPM) plays a lead role in ribosome biogenesis to stimulate RNA Pol I-dependent transcription (Li and Hann 2013) and regulates SARS-CoV, IBV, HIV-1, HCV Recruited by viral proteins to facilitate viral replication Chen et al. RPS25 deletion in yeast or mammalian cells has minimal effects on cellular protein synthesis, which implies that this ribosomal protein may be selectively required for viral IRES-mediated translation (Jack et al. Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication

abstract:
  As intracellular parasites, viruses depend heavily on host cell structures and their functions to complete their life cycle and produce new viral particles. Viruses utilize or modulate cellular translational machinery to achieve efficient replication; the role of ribosome biogenesis and protein synthesis in viral replication particularly highlights the importance of the ribosome quantity and/or quality in controlling viral protein synthesis. Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Here we summarize the recent literature on RBFs and RPs and their association with subcellular redistribution, post-translational modification, enzyme catalysis, and direct interaction with viral proteins. The advances described in this literature establish a rationale for targeting ribosome production and function in the design of the next generation of antiviral agents.


id: cord-318751-4v2tl0gi
title: Progress towards the prevention and treatment of norovirus infections
author: Arias, Armando
date: 2013-11-17
url: https://www.ncbi.nlm.nih.gov/pubmed/24199805/
doi: 10.2217/fmb.13.109
abstract:
  Noroviruses are now recognized as the major cause of acute gastroenteritis in the developed world, yet our ability to prevent and control infection is limited. Recent work has highlighted that, while typically an acute infection in the population, immunocompromised patients often experience long-term infections that may last many years. This cohort of patients and those regularly exposed to infectious material, for example, care workers and others, would benefit greatly from the development of a vaccine or antiviral therapy. While a licensed vaccine or antiviral has yet to be developed, work over the past 10 years in this area has intensified and trials with a vaccine candidate have proven promising. Numerous antiviral targets and small molecule inhibitors that have efficacy in cell culture have now been identified; however, further studies in this area are required in order to make these suitable for clinical use.


id: cord-318853-mxyxwkhx
author: Sallie, Richard
date: 2005-08-22
url: https://www.ncbi.nlm.nih.gov/pubmed/16115320/
doi: 10.1186/1743-422x-2-70
title:
  Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases

abstract:
  Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – "Viral Receptor Disease (VRD)" – may explain so-called "viral autoimmunity", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations.


id: cord-319215-8tdtia5w
author: Li, Iris W.
date: 2010-04-30
url: https://api.elsevier.com/content/article/pii/S001236921060178X
doi: 10.1378/chest.09-3072
title:
  The Natural Viral Load Profile of Patients With Pandemic 2009 Influenza A(H1N1) and the Effect of Oseltamivir Treatment

abstract:
  Background The natural history of viral shedding from the upper respiratory tract of the new pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment were uncertain. Methods A retrospective cohort study involving 145 consecutive patients with specimens positive by reverse transcriptase-polymerase chain reaction for the matrix and new H1 genes was conducted. Results The nontreated and oseltamivir-treated patients were comparable in their viral load at presentation, demography, and the presenting symptoms. No correlation was observed between viral load with age and number of symptoms. Viral load of nasopharyngeal aspirate (NPA) was significantly lower in treated than in nontreated patients at day 5 after symptom onset. When oseltamivir was initiated ≤ 2 days after symptom onset, a greater rate of viral load reduction in NPA of treated patients than that of nontreated patients was observed (−0.638 [95% CI, −0.809 to −0.466] vs −0.409 [95% CI, −0.663 to −0.185] log10 copies/mL/d post-symptom onset), and the viral load was undetectable at day 6 after oseltamivir initiation, which was 1 day earlier than that of those whose treatment was initiated > 2 days of symptom onset. The viral load was inversely correlated with concomitant absolute lymphocyte count in nontreated patients (Pearson correlation coefficient [r] = −0.687, P = .001) and treated patients (Pearson r = −0.365, P < .001). Resolution of fever was 1.4 days later in nontreated than treated patients (P = .012) Conclusions The natural viral load profile was described. Oral oseltamivir suppresses viral load more effectively when given early in mild cases of pandemic 2009 influenza A(H1N1) infections.


id: cord-319675-mwy3t1ny
author: Gu, Li
date: 2016-08-17
url: https://doi.org/10.1371/journal.pone.0160777
doi: 10.1371/journal.pone.0160777
title:
  Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia

abstract:
  The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes.


id: cord-319761-bu5pzbnv
title: Pleiotropic mechanisms of virus survival and persistence
author: Miller, Craig S.
date: 2005-07-16
txt: ./txt/cord-319761-bu5pzbnv.txt
cache: ./cache/cord-319761-bu5pzbnv.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1079210405002374
doi: 10.1016/j.tripleo.2005.03.017
summary:
  Accordingly, this review focuses on specific viral cell interactions that allow the virus to survive the cellular attack and evade the immune system, establish persistent infections, and cause chronic disease. 13, 14 Viruses regulate apoptosis by several mechanisms including the targeting of the tumor suppressor gene product p53, the Fas death receptor, and by producing caspase inhibitors and viral Bcl-2 homologs. 24, 25 The alpha herpesvirus HSV-1 encodes several antiapoptotic gene products (ie, ICP4, ICP27, c34.5, U s 3, gJ) [26] [27] [28] [29] [30] that modulate apoptosis at several levels, including antagonism of double-stranded RNA-activated protein kinase (PKR), a downstream induction molecule of the interferon signaling pathway 31, 32 Of note, all c-herpesviruses express viral homologues of cellular antiapoptotic genes, including 1 or 2 Bcl-2 homologues. In the majority of infections, viruses encode products that antagonize either the IFN signal transduction pathway or cellular proteins induced by IFN that are responsible for inhibiting virus replication (Fig 2) .

abstract:
  Viruses are enormously efficient infectious agents that have been implicated in causing human disease for centuries. Transmission of these pathogens continues to be from one life form to another in the form of isolated cases, epidemics, and pandemics. Each infection requires entry into a susceptible host, replication, and evasion of the immune system. Viruses are successful pathogens because they target specific cells for their attack, exploit the cellular machinery, and are efficient in circumventing and/or inhibiting key cellular events required of survival. This article reviews some of the advances that have taken place in human virology in the past 50 years, emphasizing mechanisms that contribute to, and are involved with, virus survival and persistence.


id: cord-320015-lbr2q4qh
title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates
author: Chinchar, V. Gregory
date: 2011-10-20
url: https://doi.org/10.3390/v3101959
doi: 10.3390/v3101959
abstract:
  Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease.


id: cord-320713-b37c8aye
title: Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery
author: Roberts, Lisa O.
date: 2009-10-27
txt: ./txt/cord-320713-b37c8aye.txt
cache: ./cache/cord-320713-b37c8aye.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1877117309900096
doi: 10.1016/s1877-1173(09)90009-6
summary:
  6 The rate of translation initiation in mammalian cells is also controlled by sequence elements within the 5 0 -and 3 0 -UTRs of mRNAs which regulate this process by providing sites for interaction of regulatory proteins and RNAs. These include upstream open reading frames (uORFs), microRNA (miRNA) target sites, and polyadenylation elements. 5 It was suggested that alternative eIF4F complexes lacking PABP could selectively promote the synthesis of viral, but not host, proteins, so that KSHV-encoded mRNAs would compete more effectively for host translation machinery in infected cells. Picornavirus translation is directed by internal ribosome entry sites (IRESs) within the 5 0 -UTRs of the viral RNAs. The central one-third of eIF4G, containing the eIF3 and one eIF4A-binding domain, is sufficient to support translation initiation from these IRESs. 43 This allows picornavirus RNAs to compete effectively for the host translation machinery following infection, although the situation appears to be more complicated than this (see Section III).

abstract:
  Viruses do not carry their own protein biosynthesis machinery and the translation of viral proteins therefore requires that the virus usurps the machinery of the host cell. To allow optimal translation of viral proteins at the expense of cellular proteins, virus families have evolved a variety of methods to repress the host translation machinery, while allowing effective viral protein synthesis. Many viruses use noncanonical mechanisms that permit translation of their own RNAs under these conditions. Viruses have also developed mechanisms to evade host innate immune responses that would repress translation under conditions of viral infection, in particular PKR activation in response to double-stranded RNA (dsRNA). Importantly, the study of viral translation mechanisms has enormously enhanced our understanding of many aspects of the cellular protein biosynthesis pathway and its components. A number of unusual mechanisms of translation initiation that were first discovered in viruses have since been observed in cellular mRNAs, and it has become apparent that a diverse range of translation mechanisms operates in eukaryotes, allowing subtle regulation of this essential process.


id: cord-323404-3mw4q7m3
title: Entry of viruses through the epithelial barrier: pathogenic trickery
author: Bomsel, Morgane
date: 2003
url: https://www.ncbi.nlm.nih.gov/pubmed/12511869/
doi: 10.1038/nrm1005
abstract:
  Mucosal surfaces — such as the lining of the gut or the reproductive tract — are the main point of entry for viruses into the body. As such, almost all viruses interact with epithelial cells, and make use of the normal epithelial signalling and trafficking pathways of the host cell. In addition to protein receptors, carbohydrate chains of proteoglycans and epithelial-membrane glycosphingolipids have emerged as a new class of receptors for viral attachment to the host cell.


id: cord-325230-3kg4oe4g
title: Viral security proteins: counteracting host defences
author: Agol, Vadim I.
date: 2010-11-09
url: https://doi.org/10.1038/nrmicro2452
doi: 10.1038/nrmicro2452
abstract:
  Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally and biochemically unrelated. Here, we consider the impact of these two proteins, as well as that of a third security protein, L(*), on viral reproduction, pathogenicity and evolution. The concept of security proteins could serve as a paradigm for the dedicated counter-defensive proteins of other viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro2452) contains supplementary material, which is available to authorized users.


id: cord-325750-x7jpsnxg
title: Metagenomics and future perspectives in virus discovery
author: Mokili, John L
date: 2012-01-20
txt: ./txt/cord-325750-x7jpsnxg.txt
cache: ./cache/cord-325750-x7jpsnxg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.coviro.2011.12.004
doi: 10.1016/j.coviro.2011.12.004
summary:
  In this article, we review virus discovery techniques with a focus on metagenomic approaches that employ high-throughput sequencing technologies to characterize novel viruses. This method lacks sufficient sensitivity to detect viruses when the viral burden is low or when the DNA sequence of the suspected etiological agent is not clearly distinguishable from the control sample [31] . The following items should be included in any report on viral metagenomic studies: firstly, the sequencing platform and its version number; secondly, raw sequence data accession numbers in a public database; thirdly, details about the bioinformatic analysis, including the homology search tool and the database being used to assign the taxonomy, and their versions; fourthly, a list of known and previously unknown viruses found, clearly showing if the ''novel'' viruses are new strains of a previously described species or completely different viruses; and fifthly, causality evidence if any.

abstract:
  Monitoring the emergence and re-emergence of viral diseases with the goal of containing the spread of viral agents requires both adequate preparedness and quick response. Identifying the causative agent of a new epidemic is one of the most important steps for effective response to disease outbreaks. Traditionally, virus discovery required propagation of the virus in cell culture, a proven technique responsible for the identification of the vast majority of viruses known to date. However, many viruses cannot be easily propagated in cell culture, thus limiting our knowledge of viruses. Viral metagenomic analyses of environmental samples suggest that the field of virology has explored less than 1% of the extant viral diversity. In the last decade, the culture-independent and sequence-independent metagenomic approach has permitted the discovery of many viruses in a wide range of samples. Phylogenetically, some of these viruses are distantly related to previously discovered viruses. In addition, 60–99% of the sequences generated in different viral metagenomic studies are not homologous to known viruses. In this review, we discuss the advances in the area of viral metagenomics during the last decade and their relevance to virus discovery, clinical microbiology and public health. We discuss the potential of metagenomics for characterization of the normal viral population in a healthy community and identification of viruses that could pose a threat to humans through zoonosis. In addition, we propose a new model of the Koch's postulates named the ‘Metagenomic Koch's Postulates’. Unlike the original Koch's postulates and the Molecular Koch's postulates as formulated by Falkow, the metagenomic Koch's postulates focus on the identification of metagenomic traits in disease cases. The metagenomic traits that can be traced after healthy individuals have been exposed to the source of the suspected pathogen.


id: cord-326273-6rp12py3
title: Detection of Severe Acute Respiratory Syndrome–Associated Coronavirus in Pneumocytes of the Lung
author: Chow, Kuan-Chih
date: 2004-04-01
url: https://www.ncbi.nlm.nih.gov/pubmed/15080310/
doi: 10.1309/c0edu0raqbtxbhce
abstract:
  Previous reports have indicated that patients with severe acute respiratory syndrome (SARS)–associated coronavirus infection could develop atypical pneumonia with fulminant pulmonary edema. However, the target cells of SARS viral infection have not been characterized in detail. We report the pathologic findings of the lung in 3 cases of SARS. Chest radiographs at 2 to 3 weeks of infection revealed an atypical pneumonia with pulmonary consolidation, a clinical characteristic of SARS infection. The presence of the SARS virus was determined by nested reverse transcription–polymerase chain reaction (RT-PCR), and the infected cells were identified by in situ hybridization in open-lung biopsy and postmortem necropsy specimens. Expression of SARS virus–encoded RNA was detected in all 3 cases by RT-PCR, and the SARS viral signal was localized in pneumocytes by using in situ hybridization.


id: cord-327444-y2464gjh
title: Meningitis, Viral
author: Wilson, M.R.
date: 2014-05-01
url: https://api.elsevier.com/content/article/pii/B9780123851574003845
doi: 10.1016/b978-0-12-385157-4.00384-5
abstract:
  This article provides an overview of the pathogenesis, epidemiology, causes, clinical presentation, laboratory diagnosis, and treatment of the most common causes of viral meningitis in the United States. It also summarizes other infectious and noninfectious causes of lymphocytic or aseptic meningitis.


id: cord-328259-3g4klpyg
title: Metagenomic Insights into the Sewage RNA Virosphere of a Large City
author: Guajardo-Leiva, Sergio
date: 2020-09-21
txt: ./txt/cord-328259-3g4klpyg.txt
cache: ./cache/cord-328259-3g4klpyg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v12091050
doi: 10.3390/v12091050
summary:
  Despite the overrepresentation of dsRNA viruses, our results show that Santiago''s sewage RNA virosphere was composed mostly of unknown sequences (88%), while known viral sequences were dominated by viruses that infect bacteria (60%), invertebrates (37%) and humans (2.4%). Viral sequences identified as Partitiviridae-like viruses included in the "unclassified RNA viruses ShiM-2016" category in the NCBI taxonomy (~25% abundance; Figure 2B ) and Totiviriade family were also highly abundant in treated and untreated sewage samples from the EU [5, 7] . Therefore, the abundance of these viruses in the Trebal metagenome can expand the known sequence space associated with this family (only 10 genomes are currently available in the NCBI database) and contribute to a better understanding of the bacteriophage biology related to RNA genomes. Taken together, our results show that metagenomic surveys of RNA viruses in sewage samples and the use of HMMs could uncover extraordinary viral diversity through the detection of remote homologs in these human-impacted environments.

abstract:
  Sewage-associated viruses can cause several human and animal diseases, such as gastroenteritis, hepatitis, and respiratory infections. Therefore, their detection in wastewater can reflect current infections within the source population. To date, no viral study has been performed using the sewage of any large South American city. In this study, we used viral metagenomics to obtain a single sample snapshot of the RNA virosphere in the wastewater from Santiago de Chile, the seventh largest city in the Americas. Despite the overrepresentation of dsRNA viruses, our results show that Santiago’s sewage RNA virosphere was composed mostly of unknown sequences (88%), while known viral sequences were dominated by viruses that infect bacteria (60%), invertebrates (37%) and humans (2.4%). Interestingly, we discovered three novel genogroups within the Picobirnaviridae family that can fill major gaps in this taxa’s evolutionary history. We also demonstrated the dominance of emerging Rotavirus genotypes, such as G8 and G6, that have displaced other classical genotypes, which is consistent with recent clinical reports. This study supports the usefulness of sewage viral metagenomics for public health surveillance. Moreover, it demonstrates the need to monitor the viral component during the wastewater treatment and recycling process, where this virome can constitute a reservoir of human pathogens.


id: cord-329162-6w8qcv1c
author: Ayginin, Andrey A.
date: 2018-08-12
txt: ./txt/cord-329162-6w8qcv1c.txt
cache: ./cache/cord-329162-6w8qcv1c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1155/2018/3248285
doi: 10.1155/2018/3248285
summary:
  The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have applied this approach to design genus-specific primer pairs for targeted enrichment of cDNA from zoonotic RNA viruses and have evaluated it using several samples from birds. The control samples cDNA was obtained by reverse transcription reaction performed on 5 L of the extracted RNA using the Reverta-L RT kit (AmpliSens; total volume of the reaction mixture is 20 L); after that 5 L of the reaction mixture containing cDNAs was further used for evaluation of the ability of the primer pair to amplify the targeted region of viruses, both in single and in multiplex PCR format.

title:
  The Study of Viral RNA Diversity in Bird Samples Using De Novo Designed Multiplex Genus-Specific Primer Panels

abstract:
  Advances in the next generation sequencing (NGS) technologies have significantly increased our ability to detect new viral pathogens and systematically determine the spectrum of viruses prevalent in various biological samples. In addition, this approach has also helped in establishing the associations of viromes with many diseases. However, unlike the metagenomic studies using 16S rRNA for the detection of bacteria, it is impossible to create universal oligonucleotides to target all known and novel viruses, owing to their genomic diversity and variability. On the other hand, sequencing the entire genome is still expensive and has relatively low sensitivity for such applications. The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. In this study, we have developed a computational pipeline for designing the oligonucleotides capable of covering a significant number of known viruses within various taxonomic orders, as well as their novel variants. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have tested our panel using a number of collected samples and have observed superior efficiency in the detection and identification of viral pathogens. Since a reliable, bioinformatics-based analytical method for the rapid identification of the sequences was crucial, an NGS-based data analysis module was developed in this study, and its functionality in the detection of novel viruses and analysis of virome diversity was demonstrated.


id: cord-329306-p5wmqmvj
title: Rhinovirus Associated Severe Respiratory Failure in Immunocompetent Adult Patient
author: Kim, Kiwook
date: 2014-09-30
txt: ./txt/cord-329306-p5wmqmvj.txt
cache: ./cache/cord-329306-p5wmqmvj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.4046/trd.2014.77.3.132
doi: 10.4046/trd.2014.77.3.132
summary:
  Rhinovirus infection is typically associated with the common cold and has rarely been reported as a cause of severe pneumonia in immunocompetent adults. Rhinovirus infection can extend to lower respiratory tract in children [4] [5] [6] or immunocompromised hosts 7, 8 , but is generally not concerned as singular cause of severe pneumonia, especially in immunocompetent adults. Although technical advances have allowed for increased detection of viral pneumonia, viral infections other than influenza are generally not considered as causes of severe respiratory tract infection in immunocompetent hosts, because viral clearance usually occurs rapidly in healthy individuals. Therefore, it is still believed that severe viral pneumonia caused by frequently exposed rhinovirus could hardly occurs in immunocompetent adults. On the contrary, our relatively young immunocompetent patient suffered severe rhinovirus pneumonia without bacterial co-infection, which was confirmed by BAL fluid analysis, and not by the nasopharyngeal specimen. Rhinovirus associated with severe lower respiratory tract infections in children

abstract:
  Rhinovirus infection is typically associated with the common cold and has rarely been reported as a cause of severe pneumonia in immunocompetent adults. A 55-year-old previous healthy woman, who consumed half a bottle of alcohol daily, presented with respiratory failure after one week of upper respiratory infection symptoms. Radiography revealed bilateral, diffuse ground glass opacity with patchy consolidation in the whole lung field; bronchoalveolar lavage fluid analysis indicated that rhinovirus was the causative organism. After five days of conservative support, the symptoms and radiographic findings began to improve. We report this rare case of rhinovirus pneumonia in an otherwise healthy host along with a review of references.


id: cord-329710-vqorb6j7
title: Exploiting Existing Molecular Scaffolds for Long-Term COVID Treatment
author: Kumar, Krishna
date: 2020-05-27
txt: ./txt/cord-329710-vqorb6j7.txt
cache: ./cache/cord-329710-vqorb6j7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1021/acsmedchemlett.0c00254
doi: 10.1021/acsmedchemlett.0c00254
summary:
  We highlight past and recent findings in essential coronavirus proteins, including RNA polymerase machinery, proteases, and fusion proteins, that offer opportunities for the design of novel inhibitors of SARS-CoV-2 infection. Many recent scientific reviews and essays have outlined vaccine efforts, as well as viral and host targets that are the focus of current campaigns aimed at redirecting clinically used compounds for COVID-19. The FDA-approved COVID-19 drug, remdesivir, is a nucleotide analog originally developed to treat Ebola infections (caused by another single-stranded RNA virus) and recently shown to inhibit the SARS-CoV-2 RdRP. HIV protease inhibitors lopinavir and ritonavir, included in the SOLIDARITY trial despite mixed reviews in the clinic, have been predicted to bind SARS-CoV-1 and CoV-2 3CL pro (96% sequence identity) based on computational studies. Using a recently solved crystal structure of the HR1 and HR2 domains of the SARS-CoV-2 S protein, lipidated peptide fusion inhibitors have been designed that inhibit pseudovirus infection of cells with IC 50 values in the single-digit nanomolar range.

abstract:
  [Image: see text] Discovery and development of COVID-19 prophylactics and treatments remains a global imperative. This perspective provides an overview of important molecular pathways involved in the viral life cycle of SARS-CoV-2, the infectious agent of COVID-19. We highlight past and recent findings in essential coronavirus proteins, including RNA polymerase machinery, proteases, and fusion proteins, that offer opportunities for the design of novel inhibitors of SARS-CoV-2 infection. By discussing the current inventory of viral inhibitors, we identify molecular scaffolds that may be improved by medicinal chemistry efforts for effective therapeutics to treat current and future coronavirus-caused diseases.


id: cord-330200-l6bnxi40
author: Huang, Jianping
date: 2020-04-27
txt: ./txt/cord-330200-l6bnxi40.txt
cache: ./cache/cord-330200-l6bnxi40.txt
extension: .txt
mime: text/plain
url: http://medrxiv.org/cgi/content/short/2020.04.22.20071258v1?rss=1
doi: 10.1101/2020.04.22.20071258
summary:
  title: Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. Only two articles report dynamics of SARS-CoV-2 viral RNA and antibodies with serial samples, but the observation periods are within 30 days. In this study, we investigated the profiles of viral RNA, IgM, and IgG in a group of patients with confirmed SARS-CoV-2 pneumonia over an 8-week period after symptom onset. Demographic data, symptom onset time, clinical features, radiological findings, routine laboratory results, and the results of SARS-CoV-2 viral RNA in throat swabs, sputum, and stool samples were recorded during hospitalization and follow-up. We investigated the serial viral load and dynamics of antibodies from patients infected with SARS-CoV-2 over an eight-week period following the onset of symptoms.

title:
  Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study

abstract:
  ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. DESIGN Retrospective, observational case series. SETTING Wenzhou Sixth Peoples Hospital PARTICIPANTS Thirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020. MAIN OUTCOME MEASURES Throat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed. RESULTS At the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients. CONCLUSION This study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence.


id: cord-330684-3hxau5vt
title: Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis
author: Richard, A
date: 2012-03-08
txt: ./txt/cord-330684-3hxau5vt.txt
cache: ./cache/cord-330684-3hxau5vt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22402601/
doi: 10.1038/cddis.2012.18
summary:
  Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Based on the well-described case of AMDV, we can In some cases, apoptosis induction by the host cell leads to exactly what is expected, namely viral attenuation, but surprisingly with the help of viral protein cleavages. However H-1PV is able to activate caspases in non-transformed cells, leading to the cleavage of NS1, a non-structural protein (NS) notably involved in viral DNA replication and gene expression by transactivating P38 promoter, which controls the synthesis of capsid proteins. In HRT18jap1 cells, the infection causes apoptosis but is not productive, suggesting that caspase activation (and possibly N caspase cleavage) prevents progeny virion generation. Induction of caspase activation and cleavage of the viral nucleocapsid protein in different cell types during Crimean-Congo hemorrhagic fever virus infection

abstract:
  Viral infection constitutes an unwanted intrusion that needs to be eradicated by host cells. On one hand, one of the first protective barriers set up to prevent viral replication, spread or persistence involves the induction of apoptotic cell death that aims to limit the availability of the cellular components for viral amplification. On the other hand, while they completely depend on the host molecular machinery, viruses also need to evade the cellular responses that are meant to destroy them. The existence of numerous antiapoptotic products within the viral kingdom proves that apoptosis constitutes a major threat that should better be bypassed. Among the different strategies developed to deal with apoptosis, one is based on what viruses do best: backfiring the cell on itself. Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Caspase cleavage of these proteins results in various consequences, from logical apoptosis inhibition to more surprising enhancement or attenuation of viral replication. The present review aims at discussing the characterization and relevance of this post-translational modification that adds a new complexity in the already intricate host–apoptosis–virus triangle.


id: cord-331673-xv1tcugl
title: Hard Nanomaterials in Time of Viral Pandemics
author: Reina, Giacomo
date: 2020-07-15
txt: ./txt/cord-331673-xv1tcugl.txt
cache: ./cache/cord-331673-xv1tcugl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1021/acsnano.0c04117
doi: 10.1021/acsnano.0c04117
summary:
  For instance, in the case of Herpesviridae and Paramyxoviridae viruses (both enveloped viruses with embedded viral-encoded glycoproteins), AgNPs can effectively reduce their infectivity, by blocking the interaction between the viral particles and the host cells with an antiviral activity strictly dependent on the size and ζ potential of the AgNPs. As a general observation, it was reported that smaller nanoparticles have better antiviral effect. cAgNPs could reduce cytopathic effects induced by RSV and showed efficient antiviral activity against infection by directly inactivating the virus prior to entry into the host cells. have reported that porous AuNPs are able to inhibit influenza A infection more efficiently than nonporous AuNPs. 39 This effect has been associated with the higher surface area of the porous material that favors their interaction with capsids and thus increases their antiviral activity ( Figure 4 ).

abstract:
  [Image: see text] The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.


id: cord-332632-u2ud0vmq
title: What can pestiviral endonucleases teach us about innate immunotolerance?
author: Lussi, Carmela
date: 2016-03-17
txt: ./txt/cord-332632-u2ud0vmq.txt
cache: ./cache/cord-332632-u2ud0vmq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27021825/
doi: 10.1016/j.cytogfr.2016.03.003
summary:
  In particular, the unique extension of ''self'' to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host''s own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Thus, the survival strategy of BVDV consists of being non-cytopathogenic and producing less dsRNA than its cp counterpart, and expressing the IFN antagonists N pro as the first protein in order to reduce or even avoid IFN production in infected cells and E rns to degrade immunostimulatory viral RNA before they might activate the host''s PRRs. Notably, both pestiviral IFN antagonists are not only required to constantly maintain innate immunotolerance during persistent infections, but they also play an important role in acute infections [25] .

abstract:
  Pestiviruses including bovine viral diarrhea virus (BVDV), border disease virus (BDV) and classical swine fever virus (CSFV), occur worldwide and are important pathogens of livestock. A large part of their success can be attributed to the induction of central immunotolerance including B- and T-cells upon fetal infection leading to the generation of persistently infected (PI) animals. In the past few years, it became evident that evasion of innate immunity is a central element to induce and maintain persistent infection. Hence, the viral non-structural protease N(pro) heads the transcription factor IRF-3 for proteasomal degradation, whereas an extracellularly secreted, soluble form of the envelope glycoprotein E(rns) degrades immunostimulatory viral single- and double-stranded RNA, which makes this RNase unique among viral endoribonucleases. We propose that these pestiviral interferon (IFN) antagonists maintain a state of innate immunotolerance mainly pertaining its viral nucleic acids, in contrast to the well-established immunotolerance of the adaptive immune system, which is mainly targeted at proteins. In particular, the unique extension of ‘self’ to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host’s own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. This mechanism of “innate tolerance” might thus provide a new facet to the role of extracellular RNases in the sustained prevention of the body’s own immunostimulatory RNA to act as a danger-associated molecular pattern that is relevant across various species.


id: cord-334010-gxu0refq
title: Viral glycoproteins: biological role and application in diagnosis
author: Banerjee, Nilotpal
date: 2016-01-18
txt: ./txt/cord-334010-gxu0refq.txt
cache: ./cache/cord-334010-gxu0refq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26925438/
doi: 10.1007/s13337-015-0293-5
summary:
  The sema-domain is the [18, 43] Fusion with host cell membrane Sialic Acid and attachment [43] 3-5 million cases Worldwide [78, 105] SARS-CoV Spike(S) glycoprotein [25, 115] Membrane fusion [115] 8422 within the duration of 1st November 2002 to 7th August 2003 occurring worldwide [113, 114] Hepatitis C virus E1 and E2 [55, 98] Binding to Host receptor and Conformational change necessary for membrane fusion [98] 130 to 150 million people globally [103, 106] Human immunodeficiency virus 1 gp120, gp160, gp41 [16] Intracellular transport [16] 35 million globally up to 2013 [83, 104, 108, 112] Zaire Ebola virus Spike Protein Gp1-Gp2 [64] Primary Host cell activation [64] up to 28th June 2015 total 27,550 cases [107, 110, 111] Dengue virus E (dimer) [64] Host cell fusion and attachment [64] WHO reported recently that there are 390 million dengue infections per year globally [109] .

abstract:
  The viruses that infect humans cause a huge global disease burden and produce immense challenge towards healthcare system. Glycoproteins are one of the major components of human pathogenic viruses. They have been demonstrated to have important role(s) in infection and immunity. Concomitantly high titres of antibodies against these antigenic viral glycoproteins have paved the way for development of novel diagnostics. Availability of appropriate biomarkers is necessary for advance diagnosis of infectious diseases especially in case of outbreaks. As human mobilization has increased manifold nowadays, dissemination of infectious agents became quicker that paves the need of rapid diagnostic system. In case of viral infection it is an emergency as virus spreads and mutates very fast. This review encircles the vast arena of viral glycoproteins, their importance in health and disease and their diagnostic applications.


id: cord-334127-wjf8t8vp
title: NCBI Viral Genomes Resource
author: Brister, J. Rodney
date: 2015-01-28
txt: ./txt/cord-334127-wjf8t8vp.txt
cache: ./cache/cord-334127-wjf8t8vp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25428358/
doi: 10.1093/nar/gku1207
summary:
  This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. Whereas primary databases are archival repositories of sequence data, reference databases provide curated datasets that enable a number of activities, among them are transfer annotation to related genomes (11) (12) (13) , sequence assembly and virus discovery (14) (15) (16) (17) , viral dynamics and evolution (18) (19) (20) and pathogen detection (14, (21) (22) (23) . The second model captures and standardizes host information for all viruses, and whenever a new RefSeq record is created, a manually curated ''viral host'' property is assigned to the relevant species within the NCBI Taxonomy database. The link to the Retrovirus Resource (http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses) provides access to the Retrovirus Genotyping Tool and HIV-1, Human Interaction Database (50, 51) .

abstract:
  Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets.


id: cord-337361-salby0fu
author: Bujarski, Jozef J.
date: 2013-03-26
txt: ./txt/cord-337361-salby0fu.txt
cache: ./cache/cord-337361-salby0fu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23533000/
doi: 10.3389/fpls.2013.00068
summary:
  In some viruses, the frequency of homologous crossing-over is very high and practically every replicated viral RNA molecule can be considered as chimerical in nature, as we have demonstrated for brome mosaic virus (BMV) RNAs (Urbanowicz et al., 2005) . The generally accepted mechanism of RNA recombination is currently explained by a copy-choice model where the viral RNA polymerase (RdRp) complex in mRNA viruses [reverse transcriptase (RT) in retroviruses] changes templates during synthesis of the nascent strand (Galetto et al., 2006) . Among the factors known to promote replicase to switch are sequence homologies between recombination substrates along with secondary structures at the crossover sites, as demonstrated with the BMV and other systems (Figlerowicz and Bujarski, 1998; Nagy et al., 1999b) . Comparison among three plant RNA virus replication systems (TBSV, BMV, and dianthoviruses) reveals general patterns within the stepwise process of viral replicase complex assembly which requires concerted involvement of protein-protein, RNA-protein, and protein-lipid interactions (Mine and Okuno, 2012) .

title:
  Genetic recombination in plant-infecting messenger-sense RNA viruses: overview and research perspectives

abstract:
  RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA–RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (1) How various factors modulate the ability of viral replicase to switch templates, (2) What is the intracellular location of RNA–RNA template switchings, (3) Mechanisms and factors responsible for non-replicative RNA recombination, (4) Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.


id: cord-337636-3yc0ribg
title: A novel two-step, direct-to-PCR method for virus detection off swabs using human coronavirus 229E
author: Morehouse, Zachary P.
date: 2020-08-25
txt: ./txt/cord-337636-3yc0ribg.txt
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mime: text/plain
url: https://doi.org/10.1186/s12985-020-01405-y
doi: 10.1186/s12985-020-01405-y
summary:
  Herein, we have developed a method to detect virus off swabs using solely shaker-mill based mechanical lysis and the transfer of the viral lysate directly to a PCR assay for virus detection, bypassing the substantial reagent and time investments required for extraction and purification steps. Swabs were spiked in serial dilutions from 1.2 × 10(6) to 1.2 × 10(1) copies/mL and then placed in 2 mL tubes with viral transport media (VTM) to mimic the specimen collection procedures in the clinic prior to processing via shaker-mill homogenization. RESULTS: HCoV-229E in vitro spiked swabs were processed in a novel two-step, direct-to-PCR methodology for viral detection. CONCLUSION: We have proven that the shaker-mill homogenization-based two-step, direct-to-PCR procedures provides sufficient viral lysis off swabs, where the resulting lysate can be used directly in PCR for the detection of HCoV-229E. Using human coronavirus 229E (HCoV-229E) as our model organism, we developed a novel two-step methodology of optimized shaker-mill homogenization parameters that allowed for direct-to-PCR viral detection.

abstract:
  BACKGROUND: Currently, one of the most reliable methods for viral infection detection are polymerase chain reaction (PCR) based assays. This process is time and resource heavy, requiring multiple steps of lysis, extraction, purification, and amplification procedures. Herein, we have developed a method to detect virus off swabs using solely shaker-mill based mechanical lysis and the transfer of the viral lysate directly to a PCR assay for virus detection, bypassing the substantial reagent and time investments required for extraction and purification steps. METHODS: Using Human Coronavirus 229E (HCoV-229E) as a model system, we spiked swabs in vitro for proof-of-concept testing. Swabs were spiked in serial dilutions from 1.2 × 10(6) to 1.2 × 10(1) copies/mL and then placed in 2 mL tubes with viral transport media (VTM) to mimic the specimen collection procedures in the clinic prior to processing via shaker-mill homogenization. After homogenization, 1 μL of lysate was processed using RT-qPCR for amplification of the nucleocapsid (N) gene, qualifying viral detection. RESULTS: HCoV-229E in vitro spiked swabs were processed in a novel two-step, direct-to-PCR methodology for viral detection. After running 54 swabs, we confidently determined our limit of detection to be 1.2 × 10(3) viral copies/mL with 96.30% sensitivity. CONCLUSION: We have proven that the shaker-mill homogenization-based two-step, direct-to-PCR procedures provides sufficient viral lysis off swabs, where the resulting lysate can be used directly in PCR for the detection of HCoV-229E. This finding allows for reductions in the time and resources required for PCR based virus detection in comparison to the traditional extraction-to-PCR methodology.


id: cord-337673-1nau263l
title: Antiviral applications of RNAi for coronavirus
author: Wu, Chang-Jer
date: 2006-01-24
txt: ./txt/cord-337673-1nau263l.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/16433589/
doi: 10.1517/13543784.15.2.89
summary:
  Recently, small interfering RNA (siRNA) has shown promise in the protection from viral invasion, as it can inhibit the expression of viral antigens and accessory genes as well as control the transcription and replication of the viral genome. Genes encoding vital proteins in reproducing SARS-CoV virions can be chosen for chemotherapeutic intervention (e.g., those coding for S, 3C-like protease [3CLpro], RNA-dependent RNA polymerase and possibly other gene products involved in viral-protein-mediated processes) [81] first demonstrated that siRNA was able to silence the replicase of SARS-CoV (1a region of the genome) and that this approach was effective in vitro against SARS-CoV. [82] subsequently observed that vector-based siRNAs could inhibit the replication of SARS-CoV, and showed that expression in the plasmid, pSUPER, of siRNAs specifically targeting viral RNA polymerases could block the cytopathic effects of SARS-CoV on Vero cells. [86] showed that three chemically synthesised siRNA duplexes targeting viral RNA polymerases, and one targeting the S gene potently inhibited SARS-CoV infection and replication in fetal rhesus kidney cells (FRhK-4) .

abstract:
  Until the appearance of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV) in early 2003, coronavirus infection was not considered to be serious enough to be controlled by either vaccination or specific antiviral therapy. It is now believed that the availability of antiviral drugs effective against SARS-CoV will be crucial for the control of future SARS outbreaks. Recently, RNA interference has been successfully used as a more specific and efficient method for gene silencing. RNA interference induced by small interfering RNA can inhibit the expression of viral antigens and so provides a new approach to the therapy of pathogenic viruses. This review provides an overview of current information on coronavirus and the application of small interfering RNA in viral therapeutics, with particular reference to SARS-CoV.


id: cord-338083-77re4l0w
title: Origination and consequences of bovine viral diarrhea virus diversity
author: Bolin, Steven R.
date: 2005-03-04
txt: ./txt/cord-338083-77re4l0w.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0749072003000811
doi: 10.1016/j.cvfa.2003.11.009
summary:
  The genetic diversity that occurs among isolates of BVDV is characteristic of RNA viruses that exist in nature as quasispecies (a swarm of viral mutants). However, altered base sequence in this region of the viral genome has been identified after passage of the virus in cell culture, and has been detected in viral RNA that was extracted from tissues of an infected animal [20, 21] . The selection of the antigenic variants likely occurred during the acute infection of the dams of those PI cattle and resulted in transplacental transmission of slightly different BVDV to a group of fetuses. Genetic and antigenic variability in bovine viral diarrhea virus (BVDV) isolates from Belgium Pathogenesis of primary respiratory disease induced by isolates from a new genetic cluster of bovine viral diarrhea virus type I Clinical and immunologic responses of vaccinated and unvaccinated calves to infection with a virulent type-II isolate of bovine viral diarrhea virus

abstract:
  The potential consequences of BVDV genetic and antigenic diversity are far ranging. The complexity of clinical presentations associated with BVDV likely arises from factors encoded by the virus genome. More importantly,prevention and control of BVDV may be complicated by diagnostic and immunization failure resulting from virus diversity. Evolutionary pressures will continue to drive further diversity, making control of BVDV challenging. Current and the potential for future BVDV strain diversity should be considered when designing BVDV control programs both at the individual farm and national herd level.


id: cord-338804-nreqluol
title: Viral Pathogenesis
author: Heise, M.T.
date: 2014-11-28
txt: ./txt/cord-338804-nreqluol.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128012383000799
doi: 10.1016/b978-0-12-801238-3.00079-9
summary:
  Viral interactions with these receptors can have a significant impact upon several aspects of viral pathogenesis, including determining the cell or tissue tropism of a virus or even whether a virus can efficiently infect and cause disease in a specific host species. Therefore, viruses that are defective in their ability to antagonize the host type I interferon system are often unable to replicate and spread efficiently within the host, illustrating the importance of viral immune evasion strategies in determining whether a virus will be pathogenic ( Figure 2) . (b) If the virus effectively interferes with the type I interferon response, interferon will be prevented from inducing a robust antiviral state within the host, and the virus is able to replicate to higher levels, will spread more efficiently, and may cause more severe disease. Therefore, like other aspects of viral pathogenesis, a complex series of virus-host interactions determines whether infection with cancer associated viruses ultimately results in disease development.

abstract:
  Viral pathogenesis describes the processes by which viral infections cause diseases and involves virus–host interactions at the cellular and systemic level that determine whether a virus will cause a disease, what form that disease takes, and how severe the disease will be. Though the pathogenesis of each virus is unique, there are several common points in the virus life cycle that are shared between all pathogenic viruses, and by considering these common aspects of the virus-induced disease process, we can explore some general concepts in viral pathogenesis while illustrating some of the virus specific processes that shape disease outcomes.


id: cord-339288-y8woqsii
title: Self-Replicating RNA
author: Tews, Birke Andrea
date: 2016-06-11
txt: ./txt/cord-339288-y8woqsii.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27987141/
doi: 10.1007/978-1-4939-6481-9_2
summary:
  Self-replicating RNA derived from the genomes of positive strand RNA viruses represents a powerful tool for both molecular studies on virus biology and approaches to novel safe and effective vaccines. Three years later, the performance of poliovirus cDNA clones could be significantly ameliorated through the introduction of SV40 transcription and replication signals and transfection of the resulting construct into cells expressing the SV40 large T antigen [14] , thus ensuring replication of the DNA-plasmid in eukaryotic cells leading to a higher yield of viral RNA and recovered virus (Fig. 2, left part) . The resulting virus CP7_E2alf was only able to infect pigs and thus displayed the Fig. 3 Generation of a chimeric viral genome from two parental RNAs. On the level of a cDNA construct, one protein-coding sequence is replaced by the corresponding gene of the other virus (principle used for the pestivirus vaccine CP7_E2alf [58] ).

abstract:
  Self-replicating RNA derived from the genomes of positive strand RNA viruses represents a powerful tool for both molecular studies on virus biology and approaches to novel safe and effective vaccines. The following chapter summarizes the principles how such RNAs can be established and used for design of vaccines. Due to the large variety of strategies needed to circumvent specific pitfalls in the design of such constructs the technical details of the experiments are not described here but can be found in the cited literature.


id: cord-340423-f8ab7413
title: Genetic Instability of RNA Viruses
author: Barr, J.N.
date: 2016-09-09
txt: ./txt/cord-340423-f8ab7413.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128033098000021
doi: 10.1016/b978-0-12-803309-8.00002-1
summary:
  We then discuss evidence that at least some RNA viruses have a replication fidelity that is poised to maximize genome sequence space without incurring catastrophic lethal mutations and describe how this can be exploited to control viral infections. The error-prone nature of polymerase activity, coupled with the absence of a proofreading mechanism, is the key reason why RNA virus genomes acquire mutations and exist as a swarm of genetic variants. The mutation rate of the viral polymerase, coupled with the replication mode that the virus employs (and extrinsic factors, described in the following text) will determine the extent of genetic variability of viruses released from an infected cell. Thus, it is possible that the high mutation rates of RNA viruses are simply a consequence of polymerases that are under selective pressure to replicate genomes very rapidly to ensure efficient viral infection [79] [80] [81] .

abstract:
  Despite having very limited coding capacity, RNA viruses are able to withstand challenge of antiviral drugs, cause epidemics in previously exposed human populations, and, in some cases, infect multiple host species. They are able to achieve this by virtue of their ability to multiply very rapidly, coupled with their extraordinary degree of genetic heterogeneity. RNA viruses exist not as single genotypes, but as a swarm of related variants, and this genomic diversity is an essential feature of their biology. RNA viruses have a variety of mechanisms that act in combination to determine their genetic heterogeneity. These include polymerase fidelity, error-mitigation mechanisms, genomic recombination, and different modes of genome replication. RNA viruses can vary in their ability to tolerate mutations, or “genetic robustness,” and several factors contribute to this. Finally, there is evidence that some RNA viruses exist close to a threshold where polymerase error rate has evolved to maximize the possible sequence space available, while avoiding the accumulation of a lethal load of deleterious mutations. We speculate that different viruses have evolved different error rates to complement the different “life-styles” they possess.


id: cord-342133-khrljehj
title: Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease
author: Principi, Nicola
date: 2015-08-12
txt: ./txt/cord-342133-khrljehj.txt
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mime: text/plain
url: https://doi.org/10.1371/journal.pone.0135640
doi: 10.1371/journal.pone.0135640
summary:
  To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). To evaluate the circulation of the different hBoV types and the possible relationships between viral load, virus genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children attending the emergency room of the Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection arising between November 1 and March 31 during 3 winters (2009-2010, 2011-2012, and 2013-2014) . Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children

abstract:
  To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1–2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.


id: cord-342660-xigv4u3f
title: In-depth virological assessment of kidney transplant recipients with COVID-19
author: Benotmane, I.
date: 2020-06-19
txt: ./txt/cord-342660-xigv4u3f.txt
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url: http://medrxiv.org/cgi/content/short/2020.06.17.20132076v1?rss=1
doi: 10.1101/2020.06.17.20132076
summary:
  We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. We thus conducted a retrospective cohort study in kidney transplant recipients (KTR) in Alsace, Grand-Est France, to determine the dynamics of nasopharyngeal and plasma viral loads and SARS-CoV-2 serology and to study their association with mortality and severe forms of COVID-19. . https://doi.org/10.1101/2020.06.17.20132076 doi: medRxiv preprint positive viral load greater than 3 log10 copies/reaction after D10, and ten patients (24.4 %) In this retrospective study conducted in a sample of 40 immunocompromised KTR hospitalized for COVID-19, we precisely determined the temporal evolution of nasopharyngeal and plasma SARS-CoV-2 loads, as well as the serological response to the virus. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China

abstract:
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies the second week after symptom onset that persisted for two months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.


id: cord-343377-6muareue
title: Viral Infections in Neonates with Suspected Late-Onset Bacterial Sepsis—A Prospective Cohort Study
author: Kidszun, André
date: 2016-05-16
txt: ./txt/cord-343377-6muareue.txt
cache: ./cache/cord-343377-6muareue.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27182999/
doi: 10.1055/s-0036-1584150
summary:
  Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Bennett et al performed a surveillance study of viral respiratory infections in two NICUs. All infants of a gestational age < 33 weeks were tested twice a week using multiplex RT-PCR ELISA. Detection of respiratory viral infections in neonates treated for suspicion of nosocomial bacterial sepsis: a feasibility study Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study Unrecognized viral respiratory tract infections in premature infants during their birth hospitalization: a prospective surveillance study in two neonatal intensive care units Viral respiratory tract infections in the Neonatal Intensive Care Unit

abstract:
  Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial virus (RSV), influenza virus A and B, H1N1 virus, parainfluenza virus 1 to 4, metapneumovirus, coronavirus, and picornavirus. Stools were examined for adenovirus, rotavirus, norovirus, and enterovirus. Results Between August 2010 and March 2014, data of 88 infants with 137 episodes of suspected late-onset bacterial sepsis were analyzed. Six infants were diagnosed with a respiratory viral infection (2 × RSV, 4 × picornavirus). Blood culture–proven bacterial sepsis was detected in 15 infants. Neither viral–bacterial coinfections nor polymerase chain reaction positive stool samples were found. Conclusion Respiratory viruses can be detected in a considerable number of neonates with suspected late-onset bacterial sepsis. In contrast, gastrointestinal viral or enterovirus infections appear uncommon in such cases.


id: cord-343470-w215pzdc
title: Epigenetic and epitranscriptomic regulation of viral replication
author: Tsai, Kevin
date: 2020-06-12
txt: ./txt/cord-343470-w215pzdc.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32533130/
doi: 10.1038/s41579-020-0382-3
summary:
  Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. First, the viral protein VP16, which is packaged into the tegument layer of incoming virions, recruits host proteins, including host-cell factor 1 (HCF-1) and octamer-binding factor (Oct-1), in order to form a complex that recruits the histone demethylases lysine-specific demethylase 1 (LSD1) and Jumonji domain 2 (JMJD2) family members as a means to remove repressive H3K9 marks from viral immediate early promoters 42 Upon entry into the cell nucleus, the DNA of many viruses initiates the replication process adjacent to subnuclear structures called pro-myelocytic leukaemia nuclear bodies (PML-NBs).

abstract:
  Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. However, viruses have evolved countermeasures that prevent the epigenetic silencing of their genes during lytic replication, and they can also take advantage of epigenetic silencing to establish latent infections. By contrast, the various covalent modifications added to RNAs, termed epitranscriptomic modifications, can positively regulate mRNA translation and/or stability, and both DNA and RNA viruses have evolved to utilize epitranscriptomic modifications as a means to maximize viral gene expression. As a consequence, both chromatin and RNA modifications could serve as novel targets for the development of antivirals. In this Review, we discuss how host epigenetic and epitranscriptomic processes regulate viral gene expression at the levels of chromatin and RNA function, respectively, and explore how viruses modify, avoid or utilize these processes in order to regulate viral gene expression.


id: cord-345168-3w32v2fm
title: Viral load in patients infected with pandemic H1N1 2009 influenza A virus
author: To, Kelvin K.W.
date: 2009-11-30
txt: ./txt/cord-345168-3w32v2fm.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19950247/
doi: 10.1002/jmv.21664
summary:
  Comparison was made between patients with pandemic H1N1 virus and seasonal influenza virus infection regarding their demographics, underlying diseases, presenting symptoms, total white blood cell counts, absolute lymphocyte counts, and initial pre-treatment viral load in respiratory specimens on the day of diagnosis. Among patients with pandemic H1N1 virus infection, the same parameters was compared between those with longer duration (!5 days) and shorter duration ( 4 days) of viral shedding, as defined by the time from onset of symptoms to the last positive sample by RT-PCR. For both pandemic H1N1 cases and seasonal influenza historical controls, respiratory specimens collected on the day of onset of symptoms (day 0) had the highest mean viral load (Fig. 1 ). For patients who presented to hospital between days 0 and 3 after onset of symptoms, the initial pre-treatment viral load in pandemic H1N1 cases was lower than the seasonal influenza historical controls.

abstract:
  Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre‐treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty‐two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 × 10(8) copies/ml for pandemic H1N1 virus compared with 3.28 × 10(8) copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT‐PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures. J. Med. Virol. 82:1–7, 2010. © 2009 Wiley‐Liss, Inc.


id: cord-346290-my8ow5ee
title: Respiratory Viral Pathogens
author: Nelson, Philipp P.
date: 2020-05-28
txt: ./txt/cord-346290-my8ow5ee.txt
cache: ./cache/cord-346290-my8ow5ee.txt
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mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128012383116356
doi: 10.1016/b978-0-12-801238-3.11635-6
summary:
  Respiratory viruses are responsible for a variety of clinical syndromes including the common cold, acute otitis media, laryngitis, sinusitis, pneumonia, bronchiolitis, influenza-like illness, and exacerbations of asthma and chronic obstructive pulmonary disease. Treatment modalities include over-the-counter and non-specific remedies along with a small number of specific antiviral medications such as the influenza neuraminidase inhibitors or palivizumab against respiratory syncytial virus. Viruses of the family of Pneumoviridae form enveloped, spherical or filamentous virions with 100-200 nm in diameter, which contain a single, linear, negative-sense RNA genome. Human bocavirus 1 (HBoV1), a member of the species Primate bocaparvovirus 1, in the genus Bocaparvovirus and the subfamily of Parvovirinae, is strongly associated with upper and lower respiratory tract infections in young children. The common cold is a rather benign clinical entity, which may however be complicated by secondary bacterial infections, otitis media, sinusitis, pneumonia, and asthma exacerbations; severe courses of disease and death may occur in young children and immunocompromised patients.

abstract:
  Respiratory viruses are responsible for a variety of clinical syndromes including the common cold, acute otitis media, laryngitis, sinusitis, pneumonia, bronchiolitis, influenza-like illness, and exacerbations of asthma and chronic obstructive pulmonary disease. Diagnosis of respiratory viral infections is primarily clinical and is further supported by laboratory techniques such as antigen detection, serology, and nucleic acid detection. Preventive strategies are based on avoidance of risk factors and, in case of influenza, vaccination. Treatment modalities include over-the-counter and non-specific remedies along with a small number of specific antiviral medications such as the influenza neuraminidase inhibitors or palivizumab against respiratory syncytial virus.


id: cord-346916-jj4l9ydl
title: Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell
author: Girardi, Erika
date: 2020-08-23
txt: ./txt/cord-346916-jj4l9ydl.txt
cache: ./cache/cord-346916-jj4l9ydl.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1084952120300914
doi: 10.1016/j.semcdb.2020.08.006
summary:
  Moreover, despite the molecular mimicry set by RNA viruses to resemble cellular mRNAs and escape host recognition, the viral nucleic acid still needs to embark on a long journey through a hostile cell environment and must overcome the obstacles put in place by the host antiviral system in order to be translated and replicated. Another example, is the zinc-finger antiviral protein (ZAP), which binds vRNAs containing a ZAP response element (ZRE) and induces RNA degradation via interaction of its N-terminal domain with host decay machinery mediated [75] (Fig. 1 ). In fact, IRES elements present in the genome of different families of RNA viruses lack overall conserved features [146, 147] .The classification of viral IRESs in four types stems from their structural organization, their respective dependence on sets of translation initiation factors, and whether they use scanning or instead directly recruit ribosomes to the start codon [148] (Fig. 2) .

abstract:
  As obligate intracellular parasites with limited coding capacity, RNA viruses rely on host cells to complete their multiplication cycle. Viral RNAs (vRNAs) are central to infection. They carry all the necessary information for a virus to synthesize its proteins, replicate and spread and could also play essential non-coding roles. Regardless of its origin or tropism, vRNA has by definition evolved in the presence of host RNA Binding Proteins (RBPs), which resulted in intricate and complicated interactions with these factors. While on one hand some host RBPs recognize vRNA as non-self and mobilize host antiviral defenses, vRNA must also co-opt other host RBPs to promote viral infection. Focusing on pathogenic RNA viruses, we will review important scenarios of RBP-vRNA interactions during which host RBPs recognize, modify or degrade vRNAs. We will then focus on how vRNA hijacks the largest ribonucleoprotein complex (RNP) in the cell, the ribosome, to selectively promote the synthesis of its proteins. We will finally reflect on how novel technologies are helping in deepening our understanding of vRNA-host RBPs interactions, which can be ultimately leveraged to combat everlasting viral threats.


id: cord-347731-eqxn6auk
author: Garcia‐Cremades, Maria
date: 2020-05-12
txt: ./txt/cord-347731-eqxn6auk.txt
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url: https://doi.org/10.1002/cpt.1856
doi: 10.1002/cpt.1856
summary:
  The data sources included were (i) longitudinal clinical, pharmacokinetic (PK), and virologic data from patients with severe acute respiratory syndrome‐2 (SARS‐CoV‐2) infection who received HCQ with or without azithromycin (n = 116), (ii) in vitro viral replication data and SARS‐CoV‐2 viral load inhibition by HCQ, (iii) a population PK model of HCQ, and (iv) a model relating chloroquine PKs to corrected QT (QTc) prolongation. 12 The drug effect over time on viral replication rate was established by simulating unbound plasma concentrations or unbound lung tissue concentrations using a previously defined partition coefficient (10 2.45 ; HCQ unbound fraction assumed to be ~ 50%) and using the established in vitro sigmoidal efficacy parameters. 3, 9, 10 Viral kinetics were estimated from in vitro replication rate of severe acute respiratory syndrome-coronavirus (SARS-CoV)-1 and unbound drug concentration in plasma and lungs were simulated with HCQ PK model.

title:
  Optimizing Hydroxychloroquine Dosing for Patients With COVID‐19: An Integrative Modeling Approach for Effective Drug Repurposing

abstract:
  Hydroxychloroquine (HCQ) is a promising candidate for Coronavirus disease of 2019 (COVID‐19) treatment. The optimal dosing of HCQ is unknown. Our goal was to integrate historic and emerging pharmacological and toxicity data to understand safe and efficacious HCQ dosing strategies for COVID‐19 treatment. The data sources included were (i) longitudinal clinical, pharmacokinetic (PK), and virologic data from patients with severe acute respiratory syndrome‐2 (SARS‐CoV‐2) infection who received HCQ with or without azithromycin (n = 116), (ii) in vitro viral replication data and SARS‐CoV‐2 viral load inhibition by HCQ, (iii) a population PK model of HCQ, and (iv) a model relating chloroquine PKs to corrected QT (QTc) prolongation. A mechanistic PK/virologic/QTc model for HCQ was developed and externally validated to predict SARS‐CoV‐2 rate of viral decline and QTc prolongation. SARS‐CoV‐2 viral decline was associated with HCQ PKs (P < 0.001). The extrapolated patient half‐maximal effective concentration (EC(50)) was 4.7 µM, comparable to the reported in vitro EC(50s). HCQ doses > 400 mg b.i.d. for ≥5 days were predicted to rapidly decrease viral loads, reduce the proportion of patients with detectable SARS‐CoV‐2 infection, and shorten treatment courses, compared with lower dose (≤ 400 mg daily) regimens. However, HCQ doses > 600 mg b.i.d. were also predicted to prolong QTc intervals. This prolongation may have clinical implications warranting further safety assessment. Due to COVID‐19's variable natural history, lower dose HCQ regimens may be indistinguishable from controls. Evaluation of higher HCQ doses is needed to ensure adequate safety and efficacy.


id: cord-349358-leicos9j
title: RNA interference for antiviral therapy
author: Ketzinel‐Gilad, Mali
date: 2006-06-16
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url: https://www.ncbi.nlm.nih.gov/pubmed/16779870/
doi: 10.1002/jgm.929
summary:
  During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Likewise, expression vectors of siRNAs specific for two different regions of the WNV genome protected 293T cells from WNV infection, and significantly reduced viral RNA replication and virus production [35] . From the reports on the use of siRNA against human viral pathogens causing acute disease, we could learn that for each specific pathogen infecting a specific cell lineage or tissue, we would probably need to perform an indepth assessment, with proper in vitro and in vivo models, and develop specific delivery systems. The most challenging part of RNAi approaches for chronic viral infections is to design the best delivery method that would facilitate the targeting of the specific organ/cells with the appropriate expression system, for durable intracellular levels of gene-silencing effect.

abstract:
  Silencing gene expression through a process known as RNA interference (RNAi) has been known in the plant world for many years. In recent years, knowledge of the prevalence of RNAi and the mechanism of gene silencing through RNAi has started to unfold. It is now believed that RNAi serves in part as an innate response against invading viral pathogens and, indeed, counter silencing mechanisms aimed at neutralizing RNAi have been found in various viral pathogens. During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Furthermore, it is now apparent that in in vitro and in some in vivo models, the prospects for this technology in developing therapeutic applications are robust. However, many key questions and obstacles in the translation of RNAi into a potential therapeutic platform still remain, including the specificity and longevity of the silencing effect, and, most importantly, the delivery of the dsRNA that induces the system. It is expected that for the specific examples in which the delivery issue could be circumvented or resolved, RNAi may hold promise for the development of gene‐specific therapeutics. Copyright © 2006 John Wiley & Sons, Ltd.


id: cord-353297-jizitnfl
title: Viruses and Bioterrorism
author: Meyer, R.F.
date: 2008-07-30
txt: ./txt/cord-353297-jizitnfl.txt
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url: https://api.elsevier.com/content/article/pii/B9780123744104005495
doi: 10.1016/b978-012374410-4.00549-5
summary:
  The requirements for an ideal biological warfare agent include availability, ease of production, stability after production, a susceptible population, absence of specific treatment, ability to incapacitate or kill the host, appropriate particle size in aerosol so that the virus can be carried long distances by prevailing winds and inhaled deeply into the lungs of unsuspecting victims, ability to be disseminated via food or water, and the availability of a vaccine to protect certain groups. Instead, the ectromelia virus vector expressing IL-4 altered the host''s immune response to this virus resulting in lethal infections in normally genetically Classification of viral agents that are considered to be of concern for bioterrorism and biowarfare and those that have been weaponized or studied for offensive or defensive purposes as part of former or current national biological weapons programs resistant mice (e.g., C57BL/6).

abstract:
  The use of viral agents for biological warfare has a long history, which predates their recognition and isolation by culture. Advances in viral culture and virus stabilization made during the second half of the twentieth century raised the level of concern by facilitating the large-scale production of viral agents for aerosol dissemination. Furthermore, the nucleic acid of many viruses, including some that are currently not threats, can be manipulated in the laboratory. Thus, the potential for genetic engineering and misuse of biotechnology is a serious threat. An effective defense against viral agents requires a comprehensive approach including restricting access to viral stocks, detecting deliberately induced disease outbreaks, rapid laboratory identification of viral agents in clinical specimens, preventing person-to-person transmission, using reliable decontamination procedures, and developing effective vaccines and antiviral drugs.


id: cord-353554-98uzivsk
author: Zhang, Zheng
date: 2018-03-08
txt: ./txt/cord-353554-98uzivsk.txt
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mime: text/plain
url: https://doi.org/10.1101/271171
doi: 10.1101/271171
summary:
  title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. 64 The virus-receptor interaction was reported to be a principal determinant of viral host 65 range, tissue tropism and cross-species infection [11, 16, 22] . However, we found the viral receptor tended not to interact with each 248 other ( Figure S3D 270 Since the virus has to compete with other proteins for binding to the receptor, proteins (Table S5) .

title:
  Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors

abstract:
  Receptor mediated entry is the first step for viral infection. However, the relationship between viruses and receptors is still obscure. Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. Additionally, the receptors used by the same virus tended to co-evolve. Further correlation analysis between viral receptors and the tissue and host specificity of the virus shows that the virus receptor similarity was a significant predictor for mammalian virus cross-species. This work could deepen our understanding towards the viral receptor selection and help evaluate the risk of viral zoonotic diseases.


id: cord-353609-no3mbg5d
title: An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses
author: Vandegrift, Kurt J.
date: 2011-04-15
txt: ./txt/cord-353609-no3mbg5d.txt
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mime: text/plain
url: https://doi.org/10.3390/v3040379
doi: 10.3390/v3040379
summary:
  Conducting viral surveillance in animal reservoirs and invertebrate vectors can help explain circulation within host species; observed patterns of zoonotic transmission; and even allow for the prediction of periods of increased risk of zoonotic transmission (e.g., Rift valley fever and rainfall [25] ; West Nile virus (WNV) and American robin (Turdus turdus) migration [26] ; as well as hantavirus in mice [27, 28] ). Globalization, host ecology, host-virus dynamics, climate change, and anthropogenic landscape changes all contribute to the complexity of zoonotic viral emergence and disease, and create significant conservation and public health challenges. While the lasting efficacy of wildlife vaccination efforts has yet to be demonstrated with either endangered species or in breaking the transmission cycle of human pathogens, an increasing number of researchers are drawing attention to systems where it seems feasible [99, 103] ; demonstrating that intricate knowledge of host and virus ecology can greatly reduce the amount of vaccine coverage that is necessary to control these viruses.

abstract:
  The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.


id: cord-353810-mf753ae9
title: A novel method for the capture-based purification of whole viral native RNA genomes
author: Tan, Cedric Chih Shen
date: 2019-04-08
txt: ./txt/cord-353810-mf753ae9.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30963294/
doi: 10.1186/s13568-019-0772-y
summary:
  This report also describes a successful application of capture-based purification as a direct RNA sequencing strategy that addresses certain limitations of current strategies in sequencing RNA viral genomes. Based on the mapping rates to human and DENV1 reference genomes for pre and post-capture groups, shown in Table 2 , purification factor was calculated to be 272-fold. The minimum coverage required for variant calling was, as described above, benchmarked to that of Illumina reads so that the effectiveness of our capture-based purification method could be more accurately evaluated based on the higher error read rates of direct RNA sequencing technology. Indeed, after comparison of the postcapture and concentrated post-capture sequencing runs (Table 2) , the 2.5-fold increase in the percentage of reads mapping to DENV1 suggests that scaling our method greatly improved the signal-to-noise ratio of this particular downstream RNA assay.

abstract:
  Current technologies for targeted characterization and manipulation of viral RNA primarily involve amplification or ultracentrifugation with isopycnic gradients of viral particles to decrease host RNA background. The former strategy is non-compatible for characterizing properties innate to RNA strands such as secondary structure, RNA–RNA interactions, and also for nanopore direct RNA sequencing involving the sequencing of native RNA strands. The latter strategy, ultracentrifugation, causes loss in genomic information due to its inability to retrieve unassembled viral RNA. To address this, we developed a novel application of current nucleic acid hybridization technologies for direct characterization of RNA. In particular, we modified a current enrichment protocol to capture whole viral native RNA genomes for downstream RNA assays to circumvent the abovementioned problems. This technique involves hybridization of biotinylated baits at 500 nucleotides (nt) intervals, stringent washes and release of free native RNA strands using DNase I treatment, with a turnaround time of about 6 h 15 min. RT-qPCR was used as the primary proof of concept that capture-based purification indeed removes host background. Subsequently, capture-based purification was applied to direct RNA sequencing as proof of concept that capture-based purification can be coupled with downstream RNA assays. We report that this protocol was able to successfully purify viral RNA by 561- to 791-fold. We also report that application of this protocol to direct RNA sequencing yielded a reduction in human host RNA background by 1580-fold, a 99.91% recovery of viral genome with at least 15× coverage, and a mean coverage across the genome of 120×. This report is, to the best of our knowledge, the first description of a capture-based purification method for assays that involve direct manipulation or characterisation of native RNA. This report also describes a successful application of capture-based purification as a direct RNA sequencing strategy that addresses certain limitations of current strategies in sequencing RNA viral genomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13568-019-0772-y) contains supplementary material, which is available to authorized users.


id: cord-355872-z6vsjmxn
title: Emerging viral infections
author: Colón-López, Daisy D.
date: 2019-08-15
txt: ./txt/cord-355872-z6vsjmxn.txt
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mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128014967000101
doi: 10.1016/b978-0-12-801496-7.00010-1
summary:
  Characterization of bacterial and viral relationships in mosquito arthropods demonstrated a symbiotic relationship between the bacterium and host, limiting dengue virus infection and potentially revealing new antiviral strategies [39, 40] . The Ebola virus outbreak in West Africa resulted in 26,648 cases and 11,017 documented deaths, and genomic sequencing was applied in near real-time to provide information to aid in containing the outbreak [44, 45] . During the Ebola virus outbreak, sequence analysis of the viral genome over time demonstrated changes which could make the pathogen resistant to therapeutics such as siRNAs, phosphorodiamidate morpholino oligomers (PMOs), and antibodies [56] . This agnostic method is appropriate for identifying changes in the human transcriptome as a result of an emerging viral infection to show specific mechanisms of immune response evasion and other effects in the host''s biology at the transcriptomic level.

abstract:
  The emergence of viral infections is driven by multiple factors including changes in human behavior, population growth, reservoir host distribution, viral diversity and environmental changes. Effective surveillance methods, diagnostic assays and containment measures are pivotal to preventing widespread outbreak of a new viral infection. However, the limited understanding of some emerging viruses poses numerous challenges for effective intervention. In this chapter we discuss various genomics-based methods and strategies to overcome these inherent challenges of emerging and re-emerging viral infections with a focus on current viral threats. We also provide an outlook on the use of genomic tools in personalized medicine and potential solutions to current and foreseeable challenges.


id: cord-355913-fhvt1ht1
title: Virus Replication
author: Burrell, Christopher J.
date: 2016-11-11
txt: ./txt/cord-355913-fhvt1ht1.txt
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mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780123751560000047
doi: 10.1016/b978-0-12-375156-0.00004-7
summary:
  Little is known about what determines whether a given picornavirus positive-sense RNA molecule will be directed (1) to a replication complex (a structure bound to smooth endoplasmic reticulum), where it serves as template for transcription by RNA-dependent RNA polymerase into negative-sense RNA, or (2) to a ribosome, where it serves as mRNA for translation into protein, or (3) to a procapsid, with which it associates to form a virion. In the case of positive-sense single-stranded RNA viruses, the incoming RNA genome can bind directly to ribosomes and be translated in full or in part without the need for any prior transcription; all other forms of incoming viral RNA must first be transcribed to produce mRNA, in order to begin the process of expression of the infecting viral genome.

abstract:
  Understanding the molecular events accompanying virus replication is essential for the proper understanding and control of all virus diseases. The virus replication cycle generates new viral genomes and proteins in sufficient quantities to ensure propagation of the viral genome; this requires that the extracellular viral genome is protected from enzymatic degradation and can be introduced into further target cells for further rounds of replication. The initial recognition between virus and host is more complex than originally supposed and may involve more than one cellular receptor. A critical first intracellular step is the generation of viral mRNA by one of a limited number of strategies first described by David Baltimore. Lacking ribosomes, viruses have no means of producing protein and are reliant on the host cell for protein synthesis. Viral proteins are often modified by host cell glycosylation during or after virus assembly. Temporal regulation of intracellular events is critical in all but the very simplest of viruses, and some form of suppression of the host innate immune response is common to nearly all human viruses. Infected cells often produce non-infectious particles with incomplete genomes, and these defective interfering particles may play a role in pathogenesis. Understanding these processes will open up a range of targets for the development of novel therapies.


