# ent

id: cord-002068-e071ciil
type: PROTEIN
entity:
  mouse anti GAPDH antibody Beyotime Inst Biotech Shanghai China rabbit anti interferon regulatory factor 1 IRF 1


id: cord-000914-d0bk9gu5
type: PROTEIN
entity:
  activator protein 1 AP 1 octamer binding transcription factor 1 Oct 1 recombination signal binding protein Jkappa RBP Jκ


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-002806-mu9jt1ul
type: PROTEIN
entity:
  rabbit polyclonal antibody PA5 40909 ThermoFisher U S A MHC I mouse monoclonal antibody ab23755 Abcam UK RPS29 rabbit polyclonal antibody PA5 41744 ThermoFisher U S A IκB α rabbit polyclonal antibody


id: cord-002806-mu9jt1ul
type: PROTEIN
entity:
  Cy3 labeled goat anti mouse IgG Beyotime China and FITC conjugated goat anti rabbit IgG secondary antibody ThermoFisher U S A


id: cord-003357-4qrg6lqu
type: ORG
entity:
  Prevalence of Common Respiratory Viral Infections and Identification of Adenovirus in Hospitalized Adults


id: cord-003207-ow3aez9v
type: DNA
entity:
  Human Adenovirus Species D Genome date 2018 09 11 journal Front Microbiol DOI 10 3389 fmicb 2018 02178 sha fd80f38e8161b81dc184779877ca0bd283ac2d2d doc_id 3207 cord_uid ow3aez9v Human adenovirus HAdV infections


id: cord-003908-wbawzbhz
type: LAW
entity:
  the Law Concerning the Prevention of Infections and Medical Care for Patients of Infections of Japan


id: cord-032614-hp07ky6q
type: CELL_LINE
entity:
  Unweighted UniFrac Figure 2D Adonis P 0 001 F 5 731 R 2 0 112 and Weighted UniFrac Figure 2E P 0 001 F 13 065 R 2 0 223 Table 2 Microbes


id: cord-001933-rnjnxymc
type: DNA
entity:
  housefly Musca domestica Diptera Muscidae hytrosavirus MdSGHV Coler et al 1993 However detection of hytrosavirus like infection symptoms i e


id: cord-257656-z7zx46gd
type: DNA
entity:
  RSV 19 3 AdV 15 6 PIVs 9 5 Flu types A and B 7 6 HCoV 229 NL63 and OC43 7 1 HBoV 5 3 HEV 4 6 and HMPV 3 1


id: cord-257656-z7zx46gd
type: WORK_OF_ART
entity:
  The Emerging Role of Rhinoviruses in Lower Respiratory Tract Infections in Children Clinical and Molecular Epidemiological Study From Croatia 2017


id: cord-252772-f3fctcru
type: DNA
entity:
  SOCS1 and miR 30c 5p levels Error bars mean SEM n 3 independent experiments P 0 05 P 0 01 P 0 001 and NS not significant infection Figure 3E


id: cord-260336-kwzo8puo
type: ORG
entity:
  Shanghai Public Health Clinical Center Animal Welfare and Ethics Committee Institutional Laboratory Animal Care and Use Committee


id: cord-264071-hg0qslyx
type: CELL_LINE
entity:
  UPGMA Unweighted Pair Group Method with Arithmetic mean also known as average linkage Michener and Sokal 1957 Two way comparisons in bacterial composition using the UniFrac metric Lozupone et al 2006 were used to measure whether the microbial communities


id: cord-267960-r5m7o9dp
type: DNA
entity:
  Q5 Hot Start High Fidelity DNA Polymerase NEB United States Supplementary Table These multiplex primer sets


id: cord-263162-37fvlhuo
type: PROTEIN
entity:
  transmembrane glycoprotein NMB GPNMB cytochrome P450 1A1 CYP1A1 14 3 3 protein beta alpha YWHAB zinc finger protein511 isoform X2 ZNF511


id: cord-263162-37fvlhuo
type: PROTEIN
entity:
  mouse anti GFP monoclonal antibody mAb ZSGB Bio China or mouse anti Flag polyclonal antibody pAb CWBIO China


id: cord-263162-37fvlhuo
type: PROTEIN
entity:
  rabbit anti GPNMB polyclonal antibody rabbit anti Cyclin A polyclonal antibody 1 1000 Santa Cruz Biotechnology


id: cord-276493-hoaxv5e0
type: PROTEIN
entity:
  K417 V445 G446 Y449 Y453 L455 F456 Y473 A475 G476 E484 F486 N487 Y489 Q493 G496 Q489 T500 N501 G502 V503


id: cord-276493-hoaxv5e0
type: DNA
entity:
  N terminal β hairpin aa 31 50 extended nidovirus RdRpassociated nucleotidyl transferase domain NiRAN aa 117 250 interface domain aa 251 365 and


id: cord-252485-cxi3cr15
type: GGP
entity:
  IFN β and SG like structures Figure 3 Supplementary Figure S3 In all cases G3BP1 positive granular structures


id: cord-269957-vd9ctqro
type: ORG
entity:
  the Ethics Committee of the Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Peking Union Medical College


id: cord-269957-vd9ctqro
type: ORG
entity:
  the Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Peking Union Medical College


id: cord-277400-w7mvk3x4
type: DNA
entity:
  human and avian hepatitis E viruses Iflaviridae and Marnaviridae thus completing the detection of all five Picornavirales families


id: cord-278540-gy65bvot
type: PROTEIN
entity:
  mouse anti V5 tag R960 25 Invitrogen mouse anti influenza A virus M2 14C2 Abcam mouse anti GFP GF200 Nacalai Tesque or rabbit antitubulin DM1A Santa Cruz antibodies


id: cord-281836-j1r771nq
type: FAC
entity:
  the Instituto de Salud Carlos III Spanish Network for Research on Infectious Diseases RD16 0016 0011


id: cord-281836-j1r771nq
type: ORG
entity:
  Leviathan Baltimore Penguin Books Culture s Consequences Comparing Values Behaviors Institutions and Organizations Across Nations Adsorption


id: cord-281836-j1r771nq
type: WORK_OF_ART
entity:
  The Essential Rousseau The Social Contract Discourse on the Origin of Inequality Discourse on the Arts and Sciences


id: cord-284889-hth8nf5b
type: DISEASE
entity:
  asthma Respiratory syncytial virus and parainfluenza virus Respiratory syncytial virus in Mandell Douglas


id: cord-289623-7oc1ykds
type: ORG
entity:
  Long Term Heavy Metal Exposure Driving Carriage of Antibiotic Resistance in Environmental Opportunistic Pathogens A Comprehensive Phenomic and Genomic Assessment


id: cord-254115-hwy962a4
type: PROTEIN
entity:
  Salmonella Shigella Vibrio toxin B producer Clostridium difficile Campylobacter Clostridium perfringens Yersinia enterocolitica


id: cord-254115-hwy962a4
type: DNA
entity:
  E coli STEC stx1 stx2 Salmonella sp Shigella sp Vibrio cholerae Yersinia enterocolitica HAdV serotypes 40 and 41 NoV GI


id: cord-254115-hwy962a4
type: DISEASE
entity:
  respiratory syndrome virus PRRSV porcine circovirus type 2 PCV 2 porcine pseudorabies virus PRV classical swine fever virus CSFV


id: cord-254115-hwy962a4
type: DISEASE
entity:
  helminths Ancylostoma duodenale Ascaris lumbricoides Necator americanus and Strongyloides stercoralis


id: cord-291295-7og5umiq
type: DNA
entity:
  Viral DNA Genome date 2019 12 13 journal Front Microbiol DOI 10 3389 fmicb 2019 02879 sha d3f515c47fec377ecc7f3961948916239e4e079f doc_id 291295 cord_uid 7og5umiq Epstein Barr virus EBV nuclear antigen 1 EBNA1 mediated DNA episomal genome


id: cord-298032-3zlu8g8y
type: PROTEIN
entity:
  ORF50 transcription activator RTA ORF57 ORF59 ORF40 ORF6 ORF9 ORF K8 ORF K9 vIRF 1 ORF K2 viral interleukin 6 vIL 6 ORF74 viral G protein


id: cord-302854-buzyani0
type: CELL_LINE
entity:
  human germline B cell receptor repertoire Xiao et al 2009 Consistent with our earlier hypothesis we did not find any specific binders against the HIV


id: cord-316537-f5rto51t
type: CL
entity:
  syncytial virus human metapneumovirus rhinovirus enterovirus adenovirus bocavirus Chlamydia Mycoplasma pneumoniae human coronavirus parainfluenza virus Bordetella Bordetella


id: cord-326217-ji0njeha
type: DNA
entity:
  miR 122 date 2018 11 27 journal Front Microbiol DOI 10 3389 fmicb 2018 02949 sha 80beb71c4b247cf32525097f28568b49f71cf08b doc_id 326217 cord_uid ji0njeha Hepatitis C


id: cord-326217-ji0njeha
type: GGP
entity:
  growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma Robust hepatitis C virus


id: cord-330942-x238hq9b
type: DISEASE
entity:
  rhinovirus coronavirus respiratory syncytial virus RSV influenza virus Para influenza virus and metapneumo virus CARV infections


id: cord-353454-zq51hpjs
type: CHEMICAL
entity:
  Achromobacter Acinetobacter Agrobacterium Bacillus Brevibacterium Microbacterium Pseudomonas Xanthomonas


id: cord-353454-zq51hpjs
type: CHEMICAL
entity:
  alkaloids benzopyranones chinones flavonoids phenolic acids quinones steroids saponins tannins terpenoids tetralones xanthones


id: cord-317499-mxt7stat
type: GGP
entity:
  activin A amphiregulin matrix metalloproteinase 9 MMP9 epidermal growth factor EGF fibroblast growth factor FGF


id: cord-329003-ovnzlpa2
type: DISEASE
entity:
  calicivirus of the Lagovirus genus RHDV contains both genomic RNA gRNA and additional subgenomic RNA sequences sgRNA The genomic RNA


id: cord-336074-76ca1cfy
type: PERCENT
entity:
  Yoshinao title Fragments of Target Cells are Internalized into Retroviral Envelope Protein Expressing Cells


id: cord-315834-ashjw2xs
type: DISEASE
entity:
  influenza A FluA adenovirus AdV bocavirus human rhinovirus HRV influenza B FluB parainfluenza PIV coronavirus CoV respiratory syncytial virus A RSVA respiratory syncytial virus B RSVB enterovirus EV


id: cord-331973-avjw4kx1
type: DNA
entity:
  Art date 2018 10 18 journal Front Microbiol DOI 10 3389 fmicb 2018 02478 sha 107df8f8ca73520a287e12ed04bd7ee29cee72af doc_id 331973


id: cord-344970-ud1lhkyi
type: ORG
entity:
  Severe Infection or Death NCT04323631 Hydroxychloroquine Post Exposure Prophylaxis PEP for Household Contacts of COVID 19


id: cord-332221-6ea6gz9s
type: PROTEIN
entity:
  substrate hepatocyte growth factor HGF docking protein insulin receptor substrate IRS vascular endothelial growth factor VEGF


id: cord-332221-6ea6gz9s
type: DNA
entity:
  Xba I and Xho I restriction sites Forward 5 TGCTCTAGAATGGGAAAAATCAGCAGTCT 3 Reverse 5 CCGCTCGAGCTACATCCTGTAGTTCTTGT 3


id: cord-332221-6ea6gz9s
type: GGP
entity:
  growth factor receptors Growth differentiation and survival multiple physiological functions for insulin


id: cord-353957-0pjg25kn
type: ORG
entity:
  the Research Ethics Committee of College of Animal Science Fujian Agriculture and Forestry University Permit Number PZCASFAFU2014002


id: cord-314567-purplsjn
type: PROTEIN
entity:
  nuclear A 128 from 222 nucleolar B 43 from 222 and cytoplasmic C 150 from 222 Colored lines between proteins


id: cord-314567-purplsjn
type: PROTEIN
entity:
  serine threonine protein phosphatase catalytic subunit PP1γ protein phosphatase 1 regulatory subunit


id: cord-314567-purplsjn
type: FAC
entity:
  the Plataforma Andaluza de Bioinformática Centro de Supercomputación y Bioinformática University of Málaga


id: cord-314567-purplsjn
type: DISEASE
entity:
  liver transplantation Anzola 2004 Dustin and Rice 2007 HCV affects 80 million people worldwide and in more than 80 of the patients


id: cord-351719-xqmir1ca
type: ORG
entity:
  List N Disinfectants For Use Against SARS CoV 2 COVID 19 And Food Safety Guidance For Food Businesses


id: cord-338773-ilir895i
type: WORK_OF_ART
entity:
  Discovery of Diverse Rodent and Bat Pestiviruses With Distinct Genomic and Phylogenetic Characteristics


id: cord-295240-76ee00i0
type: DNA
entity:
  CourseSource Bioinformatics Learning Framework Small World Initiative Crowdsourcing Antibiotic Discovery


id: cord-282305-l5r67gte
type: ORG
entity:
  Crystal Structure of Refolding Fusion Core of Lassa Virus GP2 and Design of Lassa Virus Fusion Inhibitors


id: cord-347917-fmb5nyxu
type: PROTEIN
entity:
  structural protein spike S envelope E membrane M accessory proteins NS6 structural protein nucleocapsid N and accessory proteins NS7


# bib

id: cord-000708-iuo2cw23
title: Deciphering Novel Host–Herpesvirus Interactions by Virion Proteomics
author: Lippé, Roger
date: 2012-05-28
txt: ./txt/cord-000708-iuo2cw23.txt
cache: ./cache/cord-000708-iuo2cw23.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390586/
doi: 10.3389/fmicb.2012.00181
summary:
  These studies include the alphaherpesvirinae herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV; Loret et al., 2008; Kramer et al., 2011) , the betaherpesvirinae human and murine cytomegaloviruses (HCMV and MCMV, respectively; Kattenhorn et al., 2004; Varnum et al., 2004) and the gammaherpesvirinae Kaposi sarcoma herpesvirus (KSHV), gamma herpesvirus 68 (γHV68), Epstein-Barr virus (EBV), and Alcelaphine (Bortz et al., 2003; Johannsen et al., 2004; Bechtel et al., 2005; Zhu et al., 2005; Dry et al., 2008) . Cellular stress rather than stage of the cell cycle enhances the replication and plating efficiencies of herpes simplex virus type 1 ICP0-viruses Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0 Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3 Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection

abstract:
  Over the years, a vast array of information concerning the interactions of viruses with their hosts has been collected. However, recent advances in proteomics and other system biology techniques suggest these interactions are far more complex than anticipated. One particularly interesting and novel aspect is the analysis of cellular proteins incorporated into mature virions. Though sometimes considered purification contaminants in the past, their repeated detection by different laboratories suggests that a number of these proteins are bona fide viral components, some of which likely contribute to the viral life cycles. The present mini review focuses on cellular proteins detected in herpesviruses. It highlights the common cellular functions of these proteins, their potential implications for host–pathogen interactions, discusses technical limitations, the need for complementing methods and probes potential future research avenues.


id: cord-000914-d0bk9gu5
author: Conant, Katelyn L.
date: 2013-03-12
txt: ./txt/cord-000914-d0bk9gu5.txt
cache: ./cache/cord-000914-d0bk9gu5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594938/
doi: 10.3389/fmicb.2013.00035
summary:
  In this article, we highlight emerging evidence supporting the proposition that the signaling pathways anchored by Basigin/CD147 and CD36, two of the known host receptors that control Pf invasion and cyto-adherence, respectively, are also targets for functional subversion by Kaposi''s sarcoma (KS)-associated herpesvirus (KSHV), an inherently persistent cancer-associated herpesvirus that is prevalent in malaria-endemic regions. Remarkably, we have also discovered that cross-linking of CD36 on the surface of KSHV-infected cells with MC179, a recombinant peptide derived from the CIDR1α domain of PfEMP-1 that normally interacts with CD36 to mediate cyto-adherence (Ockenhouse et al., 1989 (Ockenhouse et al., , 1991 Baruch et al., 1997) , not only upregulated CD36 expression (Figure 2A ) but also reactivated the virus from latency through transcriptional activation of KSHV RTA (Figure 2B) , and that the molecular mechanisms that control this process overlap with those that putatively regulate PfEMP-1dependent EBV reactivation from latently infected cells (Chene et al., 2007) .

title:
  Dangerous liaisons: molecular basis for a syndemic relationship between Kaposi’s sarcoma and P. falciparum malaria

abstract:
  The most severe manifestations of malaria (caused by Plasmodium falciparum) occur as a direct result of parasitemia following invasion of erythrocytes by post-liver blood-stage merozoites, and during subsequent cyto-adherence of infected erythrocytes to the vascular endothelium. However, the disproportionate epidemiologic clustering of severe malaria with aggressive forms of endemic diseases such as Kaposi’s sarcoma (KS), a neoplasm that is etiologically linked to infection with KS-associated herpesvirus (KSHV), underscores the significance of previously unexplored co-pathogenetic interactions that have the potential to modify the overall disease burden in co-infected individuals. Based on recent studies of the mechanisms that P. falciparum and KSHV have evolved to interact with their mutual human host, several new perspectives are emerging that highlight a surprising convergence of biological themes potentially underlying their associated co-morbidities. Against this background, ongoing studies are rapidly constructing a fascinating new paradigm in which the major host receptors that control parasite invasion (Basigin/CD147) and cyto-adherence (CD36) are, surprisingly, also important targets for exploitation by KSHV. In this article, we consider the major pathobiological implications of the co-option of Basigin/CD147 and CD36 signaling pathways by both P. falciparum and KSHV, not only as essential host factors for parasite persistence but also as important mediators of the pro-angiogenic phenotype within the virus-infected endothelial microenvironment. Consequently, the triangulation of interactions between P. falciparum, KSHV, and their mutual human host articulates a syndemic relationship that points to a conceptual framework for prevalence of aggressive forms of KS in malaria-endemic areas, with implications for the possibility of dual-use therapies against these debilitating infections in resource-limited parts of the world.


id: cord-001726-d7iwkatn
author: Henry, Kevin A.
date: 2015-08-04
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523942/
doi: 10.3389/fmicb.2015.00755
title:
  Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold

abstract:
  For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.


id: cord-001933-rnjnxymc
author: Kariithi, Henry M.
date: 2016-02-09
txt: ./txt/cord-001933-rnjnxymc.txt
cache: ./cache/cord-001933-rnjnxymc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746320/
doi: 10.3389/fmicb.2016.00089
summary:
  Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) is a dsDNA virus whose 190 kb genome encodes more than 60 confirmed proteins (Abd-Alla et al., 2008 , 2009b Kariithi et al., 2013a) . However, detection of hytrosavirus-like infection symptoms, i.e., the salivary gland hypertrophy syndrome (SGH) in the Narcissus bulb fly Merodon equestris (Diptera; Syrphidae; Amargier et al., 1979) and in male accessory gland filaments of the parasitic wasp Diachasmimorpha longicuadata (Hymenoptera; Braconidae; Luo and Zeng, 2010) implies that the Hytrosaviridae potentially contains other members. We hypothesized that GpSGHV infection in Glossina is under the control of host-and/or virus-encoded factors (proteins/peptides) whose interactions influence the expression or lack of overt SGH symptoms. The host (and viral) proteins identified in this study are potential targets for control of GpSGHV infections in tsetse fly mass production facilities. The clear GpSGHV-induced differential modulation of SG protein expression in Glossina raises the question of what host pathways are potentially globally regulated to facilitate successful virus infection.

title:
  Comparative Analysis of Salivary Gland Proteomes of Two Glossina Species that Exhibit Differential Hytrosavirus Pathologies

abstract:
  Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) is a dsDNA virus exclusively pathogenic to tsetse flies (Diptera; Glossinidae). The 190 kb GpSGHV genome contains 160 open reading frames and encodes more than 60 confirmed proteins. The asymptomatic GpSGHV infection in flies can convert to symptomatic infection that is characterized by overt salivary gland hypertrophy (SGH). Flies with SGH show reduced general fitness and reproductive dysfunction. Although the occurrence of SGH is an exception rather than the rule, G. pallidipes is thought to be the most susceptible to expression of overt SGH symptoms compared to other Glossina species that are largely asymptomatic. Although Glossina salivary glands (SGs) play an essential role in GpSGHV transmission, the functions of the salivary components during the virus infection are poorly understood. In this study, we used mass spectrometry to study SG proteomes of G. pallidipes and G. m. morsitans, two Glossina model species that exhibit differential GpSGHV pathologies (high and low incidence of SGH, respectively). A total of 540 host proteins were identified, of which 23 and 9 proteins were significantly up- and down-regulated, respectively, in G. pallidipes compared to G. m. morsitans. Whereas 58 GpSGHV proteins were detected in G. pallidipes F(1) progenies, only 5 viral proteins were detected in G. m. morsitans. Unlike in G. pallidipes, qPCR assay did not show any significant increase in virus titers in G. m. morsitans F(1) progenies, confirming that G. m. morsitans is less susceptible to GpSGHV infection and replication compared to G. pallidipes. Based on our results, we speculate that in the case of G. pallidipes, GpSGHV employs a repertoire of host intracellular signaling pathways for successful infection. In the case of G. m. morsitans, antiviral responses appeared to be dominant. These results are useful for designing additional tools to investigate the Glossina-GpSGHV interactions.


id: cord-002068-e071ciil
title: Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo
author: Feng, Min
date: 2016-05-25
txt: ./txt/cord-002068-e071ciil.txt
cache: ./cache/cord-002068-e071ciil.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879323/
doi: 10.3389/fmicb.2016.00786
summary:
  In the current study we analyzed the transcriptional level of selected immune-response genes we had previously identified from whole-transcriptome profiling of ALV-J-induced tumors in chicken spleen samples (Li et al., 2015) . According to the transcriptome profiles of ALV-J-induced tumor spleen samples and healthy spleen samples from White (Recessive) Plymouth Rock chickens in our previous experiments (Li et al., 2015) , we analyzed the transcriptional level of related innate immune genes. Taken together these results indicated that ALV-J early infection induced no obvious antiviral innate immunity responses in chicks sampled from 1 to 7 d.p.i. However, this was not the case for late infections and there were significant increases in Type I IFN, pro-inflammatory cytokines as well as IL-10.

abstract:
  Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β, and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL-1β, and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a twofold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks. However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression.


id: cord-002085-e7xwb03g
title: DGV: Dengue Genographic Viewer
author: Yamashita, Akifumi
date: 2016-06-07
txt: ./txt/cord-002085-e7xwb03g.txt
cache: ./cache/cord-002085-e7xwb03g.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894901/
doi: 10.3389/fmicb.2016.00875
summary:
  We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. The second database is the Dengue virus genotyping database 2 (Yamashita et al., 2013) , which provides a summary table containing the DENV serotype/genotype, year and country of collection and accession number. The Dengue Virus Resource 3 facilitates the retrieval of DENV sequences deposited in GenBank according to serotype, disease symptom, host, region/country, genome region, and collection and/or release data (Resch et al., 2009) . DGV provides a search engine for the assignment of the DENV serotype, genotype, and origin country according to the most homologous sequence on the basis of a blastn search against the DENV database.

abstract:
  Dengue viruses (DENVs) and their vectors are widely distributed throughout the tropical and subtropical regions of the world. An autochthonous case of DENV was reported in Tokyo, Japan, in 2014, for the first time in 70 years. A comprehensive database of DENV sequences containing both serotype and genotype data and epidemiological data is crucial to trace DENV outbreak isolates and promptly respond to outbreaks. We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. We also implemented the web service Dengue Genographic Viewer (DGV), which shows the geographical distribution of each DENV genotype in a user-specified time span. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. DGV also shows the distribution of DENV-infected entrants to Japan by plotting epidemiological data from the Infectious Agents Surveillance Report (IASR), Japan. This overview of the DENV genotype distribution may aid in planning for the control of DENV infections. DGV is freely available online at: (https://gph.niid.go.jp/geograph/dengue/content/genomemap).


id: cord-002376-970934vm
author: Mikel, Pavel
date: 2016-12-01
txt: ./txt/cord-002376-970934vm.txt
cache: ./cache/cord-002376-970934vm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234545/
doi: 10.3389/fmicb.2016.01911
summary:
  The quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is nowadays considered as the gold standard method for detection and quantification of enteric RNA viruses such as hepatitis A virus (HAV), hepatitis E virus (HEV) or human noroviruses (NoV) (Mattison et al., 2009; Blaise-Boisseau et al., 2010; Di Pasquale et al., 2010; Vasickova et al., 2012; Hennechart-Collette et al., 2014) . The present article is a followup study of a previously published theoretical concept (Mikel et al., 2015) and describes a method of preparation of MS2 PLP carrying a specific control sequence and their use as a PCV in RT-qPCR detection and quantification of enteric RNA viruses in swab, liver tissue, serum, feces, and vegetable samples. MS2 PLP were added in the amount of 5 × 10 6 particles to the different types of matrices (swabs, liver tissue, serum, feces, and leafy green vegetables) to reveal their ability to serve as PCV in the RT-qPCR detection of enteric RNA viruses.

title:
  Preparation of MS2 Phage-Like Particles and Their Use As Potential Process Control Viruses for Detection and Quantification of Enteric RNA Viruses in Different Matrices

abstract:
  The detection and quantification of enteric RNA viruses is based on isolation of viral RNA from the sample followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). To control the whole process of analysis and in order to guarantee the validity and reliability of results, process control viruses (PCV) are used. The present article describes the process of preparation and use of such PCV– MS2 phage-like particles (MS2 PLP) – in RT-qPCR detection and quantification of enteric RNA viruses. The MS2 PLP were derived from bacteriophage MS2 carrying a unique and specific de novo-constructed RNA target sequence originating from the DNA of two extinct species. The amount of prepared MS2 particles was quantified using four independent methods – UV spectrophotometry, fluorimetry, transmission electron microscopy and a specifically developed duplex RT-qPCR. To evaluate the usefulness of MS2 PLP in routine diagnostics different matrices known to harbor enteric RNA viruses (swab samples, liver tissue, serum, feces, and vegetables) were artificially contaminated with specific amounts of MS2 PLP. The extraction efficiencies were calculated for each individual matrix. The prepared particles fulfill all requirements for PCV – they are very stable, non-infectious, and are genetically distinct from the target RNA viruses. Due to these properties they represent a good morphological and physiochemical model. The use of MS2 PLP as a PCV in detection and quantification of enteric RNA viruses was evaluated in different types of matrices.


id: cord-002795-i1qcanti
author: Yang, Jing
date: 2017-12-12
txt: ./txt/cord-002795-i1qcanti.txt
cache: ./cache/cord-002795-i1qcanti.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732990/
doi: 10.3389/fmicb.2017.02472
summary:
  Isolated pathogen was detected by polymerase chain reaction (PCR) assay, and the result showed that only GPV was positive; Genomic sequence analysis showed that this new pathogen shared 90.8-94.6% of nucleotide identity with goose parvovirus (GPV). In addition, LAMP has been considered as a time-saving, lowcost, highly specific and sensitive method (Chotiwan et al., 2017) , which can be completed within 60 min under condition of constant temperature, and it has been established to detect GPV, Muscovy duck parvovirus (MDPV), porcine parvovirus (PPV), canine parvovirus (CPV), and others targeting at VP gene (Cho et al., 2006; Chen et al., 2009; Ji et al., 2010; JinLong et al., 2010) . Quantitative loop-mediated isothermal amplification assay was carried out using different viruses including GPV, duck plague virus, duck tembusu virus, duck hepatitis virus, duck reovirus, Muscovy duck parvovirus, and H9N2-AIV to validate specificity of this method.

title:
  Development of a Quantitative Loop-Mediated Isothermal Amplification Assay for the Rapid Detection of Novel Goose Parvovirus

abstract:
  An infectious disease characterized with short bills and protruding tongues has attacked to meat ducks in China since March 2015, which has caused ducks poor growth and enormous economic losses to duck industry of China. It was eventually proved to be caused by parvovirus after pathogen isolation and identification. As the genomic sequence analysis showed, this pathogen shared 90.8–94.6% of nucleotide identity with goose parvovirus (GPV), and it was called duck-origin novel goose parvovirus (N-GPV). In this study, a quantitative loop-mediated isothermal amplification (qLAMP) assay was developed for the rapid diagnosis of N-GPV. A set of four specific primers, two inner and two outer, were designed targeting at VP3 gene, which could be completed within 60 min at 65°C in water bath or on a real-time PCR instrument for quantitative analysis. Specificity test of LAMP assay showed that there was no cross-reactivity between N-GPV and other duck pathogens, and the detection limit of qLAMP assay was 1.0 × 10(2) copies/μL. The repeatability of this method was confirmed by inter-assay and intra-assay tests with variability ranging from 0.74 to 2.25%. The results have indicated that the qLAMP assay was a simple, rapid, accurate, sensitive, and specific method for detecting N-GPV, especially on field detection.


id: cord-002806-mu9jt1ul
title: Quantitative Analysis of Cellular Proteome Alterations in CDV-Infected Mink Lung Epithelial Cells
author: Tong, Mingwei
date: 2017-12-22
txt: ./txt/cord-002806-mu9jt1ul.txt
cache: ./cache/cord-002806-mu9jt1ul.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743685/
doi: 10.3389/fmicb.2017.02564
summary:
  Many studies have reported the effects of CDV infections on the host cell proteins, such as inhibiting STAT1 and STAT2 nuclear import (Rothlisberger et al., 2010) , inducing cytokine responses in PBMCs (Nielsen et al., 2009) , and inducing lymphocytes apoptosis (Kumagai et al., 2004) . Based on iTRAQ combined with LC-MS/MS, a quantitative proteomic analysis was performed to identify differentially expressed proteins (DEPs) in mink lung epithelial cells (Mv.1.Lu cells) infected with CDV at 24 hours post infection (hpi). Therefore, we utilized an iTRAQ approach to identify the DEPs to further explore the pathogenic mechanism and immunomodulation of CDV infection through an analysis of the effects on host cell proteins in the mink. Collectively, the findings suggested that activation of the innate immune NF-κB signaling pathway and the NLR signaling pathway was involved in mink immune responses against CDV infection, and the NF-κB signaling was associated with the pathological respiratory or other symptoms FIGURE 5 | Confirmation of the iTRAQ-MS data by western blotting or real-time RT-PCR.

abstract:
  Canine distemper virus (CDV), a paramyxovirus, causes a severe highly contagious lethal disease in carnivores, such as mink. Mink lung epithelial cells (Mv.1.Lu cells) are sensitive to CDV infection and are homologous to the natural host system of mink. The current study analyzed the response of Mv.1.Lu cells to CDV infection by iTRAQ combined with LC–MS/MS. In total, 151 and 369 differentially expressed proteins (DEPs) were markedly up-regulated or down-regulated, respectively. Thirteen DEPs were validated via real-time RT-PCR or western blot analysis. Network and KEGG pathway analyses revealed several regulated proteins associated with the NF-κB signaling pathway. Further validation was performed by western blot analysis and immunofluorescence assay, which demonstrated that different CDV strains induced NF-κB P65 phosphorylation and nuclear translocation. Moreover, the results provided interesting information that some identified DEPs possibly associated with the pathogenesis and the immune response upon CDV infection. This study is the first overview of the responses to CDV infection in Mv.1.Lu cells, and the findings will help to analyze further aspects of the molecular mechanisms involved in viral pathogenesis and the immune responses upon CDV infection.


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-003207-ow3aez9v
title: Adenoviromics: Mining the Human Adenovirus Species D Genome
author: Ismail, Ashrafali M.
date: 2018-09-11
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141750/
doi: 10.3389/fmicb.2018.02178
abstract:
  Human adenovirus (HAdV) infections cause disease world-wide. Whole genome sequencing has now distinguished 90 distinct genotypes in 7 species (A-G). Over half of these 90 HAdVs fall within species D, with essentially all of the HAdV-D whole genome sequences generated in the last decade. Herein, we describe recent new findings made possible by mining of this expanded genome database, and propose future directions to elucidate new functional elements and new functions for previously known viral components.


id: cord-003239-nph2ezii
author: Zhu, Zixiang
date: 2018-09-27
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170816/
doi: 10.3389/fmicb.2018.02326
title:
  Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction

abstract:
  Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is implicated in viral infection. In this study, we observed that foot-and-mouth disease virus (FMDV) infection significantly triggered EGR1 expression. Overexpression of EGR1 suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably promoted FMDV replication. A previously reported FMDV mutant virus (with two amino acids mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was used in this study. We found that SAP mutant FMDV infection induced a higher expression of EGR1 than wildtype FMDV infection, and also triggered higher IFN-β and IFN-stimulated genes (ISGs) expression than wildtype FMDV infection. This implied a link between EGR1 and type I IFN signaling. Further study showed that overexpression of EGR1 resulted in Sendai virus (SeV)-induced IFN-stimulated response element (ISRE) and NF-κB promoter activation. In addition, the SeV-induced ISGs expression was impaired in EGR1 knockdown cells. EGR1 upregulation promoted type I IFN signaling activation and suppressed FMDV and Seneca Valley virus replication. Suppression of the transcriptional activity of EGR1 did not affect its antiviral effect against FMDV. This study reveals a new mechanism evolved by EGR1 to enhance type I IFN signaling and suppress FMDV replication.


id: cord-003261-fz8ucwwm
title: Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling
author: Freundt, Eric C.
date: 2018-10-12
txt: ./txt/cord-003261-fz8ucwwm.txt
cache: ./cache/cord-003261-fz8ucwwm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194174/
doi: 10.3389/fmicb.2018.02448
summary:
  L * is only expressed by TMEV and is important for infection of macrophages, persistence of the virus in mice and inhibiting RNase L (van Eyll and Michiels, 2000; Sorgeloos et al., 2013) , 2B * results from a frameshifting mechanism conserved in cardioviruses that regulates the ratio of structural and non-structural proteins translated over time. (2012) , which was based on Influenza virus infection and suggests that PKR triggers the formation of "antiviral stress granules" that serve as a recruitment platform for dsRNA and RIG-like helicases, thereby enhancing IFN production. Like 3C proteases of other picornaviruses that were shown to target critical factors involved in IFN induction such as RIG-I (Barral et al., 2009) , EMCV 3C was reported to cleave TRAF family member-associated NF-kB activator (TANK) in infected cells, thus disrupting the complex involving TBK1, IKKe and IRF3 and limiting type I IFN production (Huang et al., 2017) .

abstract:
  Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L(∗) disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.


id: cord-003327-pad65nww
author: Banerjee, Arinjay
date: 2018-11-22
txt: ./txt/cord-003327-pad65nww.txt
cache: ./cache/cord-003327-pad65nww.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262150/
doi: 10.3389/fmicb.2018.02863
abstract: nan
summary:
  title: Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies by Carrillo-Araujo, M., Tas, N., Alcantara-Hernandez, R. In the Genus Spiroplasma, at least two species have been identified as plant pathogens, Spiroplasma citri, the causative agent of citrus stubborn disease (Saglio et al., 1973) and Spiroplasma kunkelii, which is associated with corn stunt disease (Whitcomb et al., 1986) . Alternatively, microbiome analysis of insectivorous bats that feed on fruit eating insects could allow us to monitor phytoplasma prevalence and spread. Looking at their data from a plant disease perspective, we wondered if frugivorous and nectivorous bats could play a role in the transmission of plant pathogens. Here, we speculate upon the role of frugivorous and nectivorous bats as possible vectors of plant pathogens. jamaicensis ( Figure 1B) and Carollia perspicillata ( Figure 1C ) and nectivorous bats Leptonycteris yerbabuenae ( Figure 1D) and Glossophaga soricina (Figure 1E ) that were sampled by the authors.

title:
  Commentary: Phyllostomid bat microbiome composition is associated to host phylogeny and feeding strategies


id: cord-003357-4qrg6lqu
author: Wang, Yingchen
date: 2018-11-27
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277751/
doi: 10.3389/fmicb.2018.02919
title:
  Prevalence of Common Respiratory Viral Infections and Identification of Adenovirus in Hospitalized Adults in Harbin, China 2014 to 2017

abstract:
  Background: Respiratory infections pose a great challenge in global health, and the prevalence of viral infection in adult patients has been poorly understood in northeast China. Harbin is one of the major cities in northeast China, and more than half of any given year in Harbin is occupied by winter. To reveal the viral etiology and seasonality in adult patients from Harbin, a 4-year consecutive survey was conducted in Harbin, China. Methods: From January 2014 to December 2017, specimens were obtained from adult patients admitted to the Second Affiliated Hospital of Harbin Medical University with lower respiratory tract infections. Sputum samples were examined by direct immunofluorescence assays to detect seven common respiratory viruses, including influenza virus (type A and B), parainfluenza virus (type 1 to 3), respiratory syncytial virus and adenovirus. Adenovirus positive samples were seeded onto A549 cells to isolate viral strains. Phylogenetic analysis was conducted on the highly variable region of adenoviral hexon gene. Results: A total of 1,300 hospitalized adult patients with lower respiratory tract infections were enrolled, in which 189 patients (14.5%) were detected as having at least one viral infection. The co-infection rate in this study was 25.9% (49/189). The dominant viral pathogen from 2014 to 2017 was parainfluenza virus, with a detection rate of 7.2%, followed by influenza virus, respiratory syncytial virus and adenovirus. Based on the climate seasons determined by daily average temperature, the highest overall viral detection rate was detected in spring (22.0%, 52/236), followed by winter (13.4%, 109/813), autumn (11.4%, 13/114) and summer (10.9%, 15/137). Adenovirus type 3 strains with slight variations were isolated from positive cases, which were closely related to the GB strain from the United States, as well as the Harbin04B strain isolated locally. Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen. Climate seasons could be rational indicators for the seasonality analysis of airborne viral infections. Future surveillance on viral mutations would be necessary to reveal the evolutionary history of respiratory viruses.


id: cord-003908-wbawzbhz
author: Matsushima, Yuki
date: 2019-09-27
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777354/
doi: 10.3389/fmicb.2019.02189
title:
  Evolutionary Analysis of the VP1 and RNA-Dependent RNA Polymerase Regions of Human Norovirus GII.P17-GII.17 in 2013–2017

abstract:
  Human norovirus (HuNoV) GII.P17-GII.17 (Kawasaki2014 variant) reportedly emerged in 2014 and caused gastroenteritis outbreaks worldwide. To clarify the evolution of both VP1 and RNA-dependent RNA polymerase (RdRp) regions of GII.P17-GII.17, we analyzed both global and novel Japanese strains detected during 2013–2017. Time-scaled phylogenetic trees revealed that the ancestral GII.17 VP1 region diverged around 1949, while the ancestral GII.P17 RdRp region diverged around 2010. The evolutionary rates of the VP1 and RdRp regions were estimated at ~2.7 × 10(−3) and ~2.3 × 10(−3) substitutions/site/year, respectively. The phylogenetic distances of the VP1 region exhibited no overlaps between intra-cluster and inter-cluster peaks in the GII.17 strains, whereas those of the RdRp region exhibited a unimodal distribution in the GII.P17 strains. Conformational epitope positions in the VP1 protein of the GII.P17-GII.17 strains were similar, although some substitutions, insertions and deletions had occurred. Strains belonging to the same cluster also harbored substitutions around the binding sites for the histo-blood group antigens of the VP1 protein. Moreover, some amino acid substitutions were estimated to be near the interface between monomers and the active site of the RdRp protein. These results suggest that the GII.P17-GII.17 virus has produced variants with the potential to alter viral antigenicity, host-binding capability, and replication property over the past 10 years.


id: cord-003970-3e58229u
title: Temporal Dynamics of Co-circulating Lineages of Porcine Reproductive and Respiratory Syndrome Virus
author: Paploski, Igor Adolfo Dexheimer
date: 2019-11-01
txt: ./txt/cord-003970-3e58229u.txt
cache: ./cache/cord-003970-3e58229u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839445/
doi: 10.3389/fmicb.2019.02486
summary:
  Porcine reproductive and respiratory syndrome virus (PRRSV), the etiological agent of PRRS, is one of the most important endemic viruses affecting the swine industry in the United States (Holtkamp et al., 2013) and globally (Stadejek et al., 2013; VanderWaal and Deen, 2018) . Porcine reproductive and respiratory syndrome virus was first recognized almost simultaneously in Europe (Wensvoort et al., 1991) and North America (Collins et al., 1992) in the late 1980s and early 1990s, but genetic differences suggested a much earlier evolutionary divergence between the North American and European viral types. Here, we describe the temporal dynamics of PRRSV occurrence in a swine-dense region of the United States, characterizing these patterns according to ORF5 genetic lineages and sub-lineages. Porcine reproductive and respiratory syndrome virus diversity of Eastern Canada swine herds in a large sequence dataset reveals two hypervariable regions under positive selection

abstract:
  Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the most important endemic pathogen in the U.S. swine industry. Despite control efforts involving improved biosecurity and different vaccination protocols, the virus continues to circulate and evolve. One of the foremost challenges in its control is high levels of genetic and antigenic diversity. Here, we quantify the co-circulation, emergence and sequential turnover of multiple PRRSV lineages in a single swine-producing region in the United States over a span of 9 years (2009–2017). By classifying over 4,000 PRRSV sequences (open-reading frame 5) into phylogenetic lineages and sub-lineages, we document the ongoing diversification and temporal dynamics of the PRRSV population, including the rapid emergence of a novel sub-lineage that appeared to be absent globally pre-2008. In addition, lineage 9 was the most prevalent lineage from 2009 to 2010, but its occurrence fell to 0.5% of all sequences identified per year after 2014, coinciding with the emergence or re-emergence of lineage 1 as the dominant lineage. The sequential dominance of different lineages, as well as three different sub-lineages within lineage 1, is consistent with the immune-mediated selection hypothesis for the sequential turnover in the dominant lineage. As host populations build immunity through natural infection or vaccination toward the most common variant, this dominant (sub-) lineage may be replaced by an emerging variant to which the population is more susceptible. An analysis of patterns of non- synonymous and synonymous mutations revealed evidence of positive selection on immunologically important regions of the genome, further supporting the potential that immune-mediated selection shapes the evolutionary and epidemiological dynamics for this virus. This has important implications for patterns of emergence and re-emergence of genetic variants of PRRSV that have negative impacts on the swine industry. Constant surveillance on PRRSV occurrence is crucial to a better understanding of the epidemiological and evolutionary dynamics of co-circulating viral lineages. Further studies utilizing whole genome sequencing and exploring the extent of cross-immunity between heterologous PRRS viruses could shed further light on PRRSV immunological response and aid in developing strategies that might be able to diminish disease impact.


id: cord-003976-05tf6oqa
author: Wang, Kai
date: 2019-11-06
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851170/
doi: 10.3389/fmicb.2019.02540
title:
  Anti-TGEV Miller Strain Infection Effect of Lactobacillus plantarum Supernatant Based on the JAK-STAT1 Signaling Pathway

abstract:
  Transmissible gastroenteritis (TGE), caused by transmissible gastroenteritis virus (TGEV), is one many gastrointestinal inflections in piglets, characterized by diarrhea, and high mortality. Probiotics are ubiquitous bacteria in animal intestines, which have many functions, such as promoting intestinal peristalsis and maintaining the intestinal balance. We found that the supernatant of the Lp-1 strain of Lactobacillus plantarum, isolated in our laboratory, and named Lp-1s had marked anti-TGEV effect on IPEC-J2 cells. Lp-1s could induce large amounts of interferon-β in IPEC-J2 cells in the early stage (6 h) of infection with TGEV, and increased the level of phosphorylated signal transducer and activator of transcription and its nuclear translocation in the late stage (24–48 h) of infection. This resulted in upregulated expression of interferon-stimulated genes, and increased the transcription and protein expression of antiviral proteins, resulting in an anti-TGEV effect.


id: cord-032614-hp07ky6q
author: Minich, Jeremiah J.
date: 2020-08-24
txt: ./txt/cord-032614-hp07ky6q.txt
cache: ./cache/cord-032614-hp07ky6q.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476325/
doi: 10.3389/fmicb.2020.02015
summary:
  In this study, we characterized the microbiome of ranched southern Bluefin Tuna, Thunnus maccoyii, across four anatomic sites (gill, skin, digesta, and anterior kidney) and evaluated environmental and pathological factors that influence microbiome composition, including the impact of PZQ treatment on microbiome stability. In this study, we characterized the microbiome of ranched southern Bluefin Tuna, Thunnus maccoyii, across four anatomic sites (gill, skin, digesta, and anterior kidney) and evaluated environmental and pathological factors that influence microbiome composition, including the impact of PZQ treatment on microbiome stability. In this study, ranched SBT were sampled to characterize the microbial diversity associated with mucosal body sites, including gill, skin, and gut, providing the first assessment of microbiome diversity in this ecologically and commercially important fish species. In this study we set out to describe how the fish mucosal microbiome is associated by parasitic infection and treatment with praziquantel (PZQ) across three body sites including the gill, skin, and digesta of Southern Bluefin Tuna (SBT).

title:
  The Southern Bluefin Tuna Mucosal Microbiome Is Influenced by Husbandry Method, Net Pen Location, and Anti-parasite Treatment

abstract:
  Aquaculture is the fastest growing primary industry worldwide. Marine finfish culture in open ocean net pens, or pontoons, is one of the largest growth areas and is currently the only way to rear high value fish such as bluefin tuna. Ranching involves catching wild juveniles, stocking in floating net pens and fattening for 4 to 8 months. Tuna experience several parasite-induced disease challenges in culture that can be mitigated by application of praziquantel (PZQ) as a therapeutic. In this study, we characterized the microbiome of ranched southern Bluefin Tuna, Thunnus maccoyii, across four anatomic sites (gill, skin, digesta, and anterior kidney) and evaluated environmental and pathological factors that influence microbiome composition, including the impact of PZQ treatment on microbiome stability. Southern bluefin tuna gill, skin, and digesta microbiome communities are unique and potentially influenced by husbandry practices, location of pontoon growout pens, and treatment with the antiparasitic PZQ. There was no significant relationship between the fish mucosal microbiome and incidence or abundance of adult blood fluke in the heart or fluke egg density in the gill. An enhanced understanding of microbiome diversity and function in high-value farmed fish species such as bluefin tuna is needed to optimize fish health and improve aquaculture yield. Comparison of the bluefin tuna microbiome to other fish species, including Seriola lalandi (yellowtail kingfish), a common farmed species from Australia, and Scomber japonicus (Pacific mackerel), a wild caught Scombrid relative of tuna, showed the two Scombrids had more similar microbial communities compared to other families. The finding that mucosal microbial communities are more similar in phylogenetically related fish species exposes an opportunity to develop mackerel as a model for tuna microbiome and parasite research.


id: cord-252485-cxi3cr15
author: Yoshida, Asuka
date: 2015-08-04
txt: ./txt/cord-252485-cxi3cr15.txt
cache: ./cache/cord-252485-cxi3cr15.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2015.00804
doi: 10.3389/fmicb.2015.00804
summary:
  We and other groups have recently reported that recombinant viruses of Sendai virus (SeV), a prototype of the family Paramyxoviridae, in which the C proteins are knocked-out or mutated, generate dsRNA in infected cells at levels similar to the production of IFN-β (Takeuchi et al., 2008; Irie et al., 2010) . These unusual RNAs exhibited distinct properties in infected cells in terms of encapsidation with the viral N protein and subcellular distribution with SG marker proteins and RLRs. Our results suggest that RNA-typedependent mechanisms recognize and accumulate virus-derived, IFN-β-inducible, unusual RNAs into specific compartment to trigger the production of IFN-β, and that SeV may evade detection by the host innate immune system by preventing the production of these RNA species. Since the naked cbDI genomes have been reported readily to form an ideal structure as the RIG-I ligands of 5 -triphosphated, blunt-ended dsRNA (Kolakofsky, 1976) , these results indicated that the major IFN-β-inducing viral RNA species produced in the cells infected with CNT was encapsidated cbDI genomes, whereas those for SeV-4C(-) and NDV were not.

title:
  IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner

abstract:
  The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5′-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures.


id: cord-252772-f3fctcru
title: The Coronavirus PEDV Evades Type III Interferon Response Through the miR-30c-5p/SOCS1 Axis
author: Wang, Changlin
date: 2020-05-22
url: https://www.ncbi.nlm.nih.gov/pubmed/32574254/
doi: 10.3389/fmicb.2020.01180
abstract:
  Porcine epidemic diarrhea virus (PEDV) is an economically important pathogen that has evolved several mechanisms to evade type I IFN responses. Type III interferon (IFN-λ), an innate cytokine that primarily targets the mucosal epithelia, is critical in fighting mucosal infection in the host and has been reported to potently inhibit PEDV infection in vitro. However, how PEDV escapes IFN-λ antiviral response remains unclear. In this study, we found that PEDV infection induced significant IFN-λ expression in type I IFN-defective Vero E6 cells, but virus-induced endogenous IFN-λ did not reduce PEDV titers. Moreover, we demonstrated that PEDV escaped IFN-λ responses by substantially upregulating the suppressor of cytokine signaling protein 1 (SOCS1) expression, which impaired the induction of IFN-stimulated genes (ISGs) and dampened the IFN-λ antiviral response and facilitated PEDV replication in Vero E6 cells. We further showed that PEDV infection increased SOCS1 expression by decreasing host miR-30c-5p expression. MiR-30c-5p suppressed SOCS1 expression through targeting the 3′ untranslated region (UTR) of SOCS1. The inhibition of IFN-λ elicited ISGs expression by SOCS1 was specifically rescued by overexpression of miR-30c-5p. Collectively, our findings identify a new strategy by PEDV to escape IFN-λ-mediated antiviral immune responses by engaging the SOCS1/miR-30c axis, thus improving our understanding of its pathogenesis.


id: cord-254115-hwy962a4
title: xMAP Technology: Applications in Detection of Pathogens
author: Reslova, Nikol
date: 2017-01-25
url: https://www.ncbi.nlm.nih.gov/pubmed/28179899/
doi: 10.3389/fmicb.2017.00055
abstract:
  xMAP technology is applicable for high-throughput, multiplex and simultaneous detection of different analytes within a single complex sample. xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. As an open architecture platform, the xMAP technology is beneficial to end users and therefore it is used in various pharmaceutical, clinical and research laboratories. The main aim of this review is to summarize the latest findings and applications in the field of pathogen detection using microsphere-based multiplex assays.


id: cord-257656-z7zx46gd
author: Ljubin-Sternak, Sunčanica
date: 2019-12-03
url: https://www.ncbi.nlm.nih.gov/pubmed/31849887/
doi: 10.3389/fmicb.2019.02737
title:
  The Emerging Role of Rhinoviruses in Lower Respiratory Tract Infections in Children – Clinical and Molecular Epidemiological Study From Croatia, 2017–2019

abstract:
  Rhinoviruses (RVs) are increasingly implicated not only in mild upper respiratory tract infections, but also in more severe lower respiratory tract infections; however, little is known about species diversity and viral epidemiology of RVs among the infected children. Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. For respiratory virus detection, nasopharyngeal and pharyngeal flocked swabs were taken from each patient and subsequently analyzed with multiplex RT-PCR. To determine the RV species in a subset of positive children, 5′UTR in RV-positive samples has been sequenced. Nucleotide sequences of referent RV strains were retrieved by searching the database with Basic Local Alignment Tool, and used to construct alignments and phylogenetic trees using MAFFT multiple sequence alignment tool and the maximum likelihood method, respectively. In our study population RV was the most frequently detected virus, diagnosed in 197 patients (33.4%), of which 60.4% was detected as a monoinfection. Median age of RV-infected children was 2.25 years, and more than half of children infected with RV (55.8%) presented with lower respiratory tract infections. Most RV cases were detected from September to December, and all three species co-circulated during the analyzed period (2017–2019). Sequence analysis based on 5′UTR region yielded 69 distinct strains; the most prevalent was RV-C (47.4%) followed by RV-A (44.7%) and RV-B (7.9%). Most of RV-A sequences formed a distinct phylogenetic group; only strains RI/HR409-18 (along with a reference strain MF978777) clustered with RV-C strains. Strains belonging to the group C were the most diverse (41.6% identity among strains), while group B was the most conserved (71.5% identity among strains). Despite such differences in strain groups (hitherto undescribed in Croatia), clinical presentation of infected children was rather similar. Our results are consistent with newer studies that investigated the etiology of acute respiratory infections, especially those focused on children with lower respiratory tract infections, where RVs should always be considered as potentially serious pathogens.


id: cord-260336-kwzo8puo
author: Si, Lulu
date: 2019-09-27
txt: ./txt/cord-260336-kwzo8puo.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2019.02250
doi: 10.3389/fmicb.2019.02250
summary:
  Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Student''s unpaired two-tailed t-test was used to monitor the distribution of Z2 in male A129 mouse body and testicular tissue and to analyze the difference of viral RNA level in sera or tissues between Z2-and vehicle-treated A129 mice. ZIKV RNA copies in (A) testes, (B) epididymides, and (C) sperm of Z2-or vehicle-treated ZIKV-infected male A129 mice at day 16 were detected by qRT-PCR. Zika virus infection in the testicular tissue not only damages male testicular tissue, resulting in pathological lesion of testes and epididymides, but also produces ZIKV-infected semen, causing infertility.

title:
  A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue

abstract:
  Zika virus (ZIKV) was a re-emerging arbovirus associated with Guillain–Barré Syndrome in adult and congenital Zika syndrome in fetus and infant. Although ZIKV was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. ZIKV can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. However, no drug has been approved for prevention or treatment of ZIKV infection, especially infection in male testicular tissue. Previously reported peptide Z2 could inactivate ZIKV, inhibiting ZIKV infection in vitro and in vivo. Importantly, Z2 could inhibit vertical transmission of ZIKV in pregnant mice, reducing ZIKV infection in fetus. Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Thus, Z2, a ZIKV inactivator, could serve as an antiviral agent for treatment of ZIKV infection and attenuation of ZIKV-induced testicular tissue damage.


id: cord-262682-gsvswr7v
title: Segmented Filamentous Bacteria – Metabolism Meets Immunity
author: Hedblom, Grant A.
date: 2018-08-24
url: https://www.ncbi.nlm.nih.gov/pubmed/30197636/
doi: 10.3389/fmicb.2018.01991
abstract:
  Segmented filamentous bacteria (SFB) are a group of host-adapted, commensal organisms that attach to the ileal epithelium of vertebrate and invertebrate hosts. A genetic relative of the genus Clostridium, these morphologically unique bacteria display a replication and differentiation lifecycle initiated by epithelial tissue binding and filamentation. SFB intimately bind to the surface of absorptive intestinal epithelium without inducing an inflammatory response. Rather, their presence impacts the generation of innate and differentiation of acquired immunity, which impact the clearance of extracellular bacterial or fungal pathogens in the gastrointestinal and respiratory tracts. SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). SFB are the first commensal bacteria identified that impact the maturation and development of Th17 cells in mice. Recently, microbiome studies have revealed the presence of Candidatus Arthromitus (occasionally designated as Candidatus Savagella), a proposed candidate species of SFB, in higher proportions in higher-performing flocks as compared to matched lower-performing flocks, suggesting that SFB may serve to establish a healthy gut and protect commercial turkeys from pathogens resulting in morbidity and decreased performance. In this review we seek to describe the life cycle, host specificity, and genetic capabilities of SFB, such as bacterial metabolism, and how these factors influence the host immunity and microbiome. Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. This review demonstrates the importance of studying and further characterizing commensal, host-specific bacteria in food-producing animals and their importance to animal health.


id: cord-263162-37fvlhuo
author: Guo, Kangkang
date: 2019-01-08
url: https://www.ncbi.nlm.nih.gov/pubmed/30671053/
doi: 10.3389/fmicb.2018.03295
title:
  A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein

abstract:
  Porcine circovirus type 2 (PCV2) is the infectious agent of postweaning multisystemic wasting syndrome (PMWS). The recently discovered open reading frame 5 (ORF5) in PCV2 genome encodes a non-structural protein. Previous study revealed that ORF5 protein inhibits cell proliferation and may interact with host transmembrane glycoprotein NMB (GPNMB). However, whether the GPNMB affects PCV2 replication and the underlying molecular mechanisms are still unknown. In this study, the transcriptome maps of PCV2-infected and ORF5-transfected porcine alveolar macrophages 3D4/2 (PAM) cells were profiled. The GPNMB gene was down-regulated in PCV2-infected and ORF5-transfected PAMs. By using glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal microscopy approaches, we convincingly showed that PCV2 ORF5 protein interacts with GPNMB. Furthermore, by utilizing lentivirus mediated overexpression or knockdown approach, we showed that the cellular GPNMB significantly inhibits PCV2 replication and ORF5 expression. Moreover, GPNMB overexpressing leads to an increased Cyclin A expression and a reduced S phase, whereas GPNMB knockdown causes a decreased Cyclin A expression and a prolonged S phase. In conclusion, we identified a novel host factor GPNMB that interacts with PCV2 ORF5 protein and restricts PCV2 replication.


id: cord-264071-hg0qslyx
author: Camelo-Castillo, Anny
date: 2019-01-28
url: https://doi.org/10.3389/fmicb.2019.00011
doi: 10.3389/fmicb.2019.00011
title:
  Nasopharyngeal Microbiota in Children With Invasive Pneumococcal Disease: Identification of Bacteria With Potential Disease-Promoting and Protective Effects

abstract:
  Background and Aims: The risk of suffering from some infectious diseases can be related to specific microbiota profiles. Specifically, the nasopharyngeal microbiota could play a role as a risk or protective factor in the development of invasive disease caused by S. pneumoniae. Methodology: We analyzed the nasopharyngeal microbiota of children with invasive pneumococcal disease (IPD) and that of healthy controls matched by age, sex, and seasonality from Catalonia, Spain. Epidemiological, microbiological and clinical variables were considered to compare microbiota profiles, analyzed by sequencing the V1–V4 region of the 16S rRNA gene. Results: Twenty-eight children with IPD (median age 43 months) and 28 controls (42.6 months) were included in the study. IPD children presented a significantly higher bacterial diversity and richness (p < 0.001). Principal coordinate analysis revealed three different microbiota profiles: microbiota A, dominated by the genus Dolosigranulum (44.3%); Microbiota B, mostly represented by Streptococcus (36.9%) and Staphylococcus (21.3%) and a high diversity of anaerobic genera including Veillonella, Prevotella and Porphyromonas; and Microbiota C, mainly containing Haemophilus (52.1%) and Moraxella (31.4%). The only explanatory factor for the three microbiotas was the classification of children into disease or healthy controls (p = 0.006). A significant negative correlation was found between Dolosigranulum vs. Streptococcus (p = 0.029), suggesting a potential antagonistic effect against pneumococcal pathogens. Conclusions: The higher bacterial diversity and richness in children with IPD could suggest an impaired immune response. This lack of immune competence could be aggravated by breastfeeding <6 months and by the presence of keystone pathogens such as Porphyromonas, a bacterium which has been shown to be able to manipulate the immune response, and that could favor the overgrowth of many proteolytic anaerobic organisms giving rise to a dramatic dysbiosis. From an applied viewpoint, we found suggestive microbiota profiles associated to IPD or asymptomatic colonization that could be used as disease biomarkers or to pave the way for characterizing health-associated inhabitants of the respiratory tract. The identification of beneficial bacteria could be useful to prevent pneumococcal infections by integrating those microorganisms in a probiotic formula. The present study suggests not only respiratory tract samples, but also breast milk, as a potential source of those beneficial bacteria.


id: cord-267735-y3832u9e
author: Sun, Wuping
date: 2020-09-24
url: https://www.ncbi.nlm.nih.gov/pubmed/33072033/
doi: 10.3389/fmicb.2020.572318
abstract: nan
title:
  Management of Immunity Alteration-Induced Chronic Pain During the Coronavirus Disease-2019 (COVID-19) Pandemic


id: cord-267960-r5m7o9dp
author: Hourdel, Véronique
date: 2020-09-25
url: https://www.ncbi.nlm.nih.gov/pubmed/33101244/
doi: 10.3389/fmicb.2020.571328
title:
  Rapid Genomic Characterization of SARS-CoV-2 by Direct Amplicon-Based Sequencing Through Comparison of MinION and Illumina iSeq100(TM) System

abstract:
  Global human health is increasingly challenged by emerging viral threats, especially those observed over the last 20 years with coronavirus-related human diseases, such as the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS). Recently, in late December 2019, a novel Betacoronavirus, SARS-CoV-2, originating from the Chinese city of Wuhan, emerged and was then identified as the causative agent of a new severe form of pneumonia, COVID-19. Real-time genome sequencing in such viral outbreaks is a key issue to confirm identification and characterization of the involved pathogen and to help establish public health measures. Here, we implemented an amplicon-based sequencing approach combined with easily deployable next-generation sequencers, the small and hand-held MinION sequencer and the latest most compact Illumina sequencer, the iSeq100(TM) system. Our results highlighted the great potential of the amplicon-based approach to obtain consensus genomes of SARS-CoV-2 from clinical samples in just a few hours. Both these mobile next-generation sequencers are proven to be efficient to obtain viral sequences and easy to implement, with a minimal laboratory environment requirement, providing useful opportunities in the field and in remote areas.


id: cord-269957-vd9ctqro
author: Hua, Chen
date: 2019-09-26
url: https://doi.org/10.3389/fmicb.2019.02188
doi: 10.3389/fmicb.2019.02188
title:
  The Underlying Mechanism of 3-Hydroxyphthalic Anhydride-Modified Bovine Beta-Lactoglobulin to Block Human Papillomavirus Entry Into the Host Cell

abstract:
  We have previously demonstrated that 3-hydroxyphthalic anhydride (3HP)-modified bovine beta-lactoglobulin (3HP-β-LG) is highly effective in inhibiting entry of pseudovirus (PsV) of high- and low-risk human papillomavirus (HPV) into the target cell. Intravaginally applied 3HP-β-LG-containing vaginal gel could significantly inhibit HPV infection and reduce viral load in the cervical region. However, we still do not understand the underlying molecular mechanism by which 3HP-β-LG is able to inhibit HPV infection. Here, though, we showed that 3HP-β-LG did not inactivate HPV PsV, but rather blocked entry of HPV PsV into the target cell via its interaction with virus, not cell. It bound to the positively charged region in the HPV L1 protein, suggesting that 3HP-β-LG binds to HPV L1 protein through the interaction between the negatively charged region in 3HP-β-LG and the positively charged region in HPV L1 protein, thus competitively blocking the binding of HPV to the receptor on the basement membrane in vaginal mucosa. Although 3HP-modified chicken ovalbumin (3HP-OVA) also carries high net negative charges, it exhibited no anti-HPV activity, suggesting that the interaction between 3HP-modified protein and HPV L1 protein relies on both electrostatic and matchable conformation of the binding sites in both proteins. When topically applied, 3HP-β-LG did not enter the host cell or blood circulation. These findings suggest that 3HP-β-LG targets HPV L1 protein and blocks HPV entry into the host cell, thus being safe and effective for topical application in the treatment of HPV infection.


id: cord-271557-xic32wxh
title: Morbillivirus Receptors and Tropism: Multiple Pathways for Infection
author: Sato, Hiroki
date: 2012-03-01
url: https://www.ncbi.nlm.nih.gov/pubmed/22403577/
doi: 10.3389/fmicb.2012.00075
abstract:
  Morbilliviruses, which include measles virus (MeV), canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with two envelope proteins, one of which is hemagglutinin (H) protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150), which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although two major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.


id: cord-276493-hoaxv5e0
title: Therapeutic Strategies Against COVID-19 and Structural Characterization of SARS-CoV-2: A Review
author: Jeong, Gi Uk
date: 2020-07-14
url: https://doi.org/10.3389/fmicb.2020.01723
doi: 10.3389/fmicb.2020.01723
abstract:
  The novel coronavirus, SARS-CoV-2, or 2019-nCoV, which originated in Wuhan, Hubei province, China in December 2019, is a grave threat to public health worldwide. A total of 3,672,238 confirmed cases of coronavirus disease 2019 (COVID-19) and 254,045 deaths were reported globally up to May 7, 2020. However, approved antiviral agents for the treatment of patients with COVID-19 remain unavailable. Drug repurposing of approved antivirals against other viruses such as HIV or Ebola virus is one of the most practical strategies to develop effective antiviral agents against SARS-CoV-2. A combination of repurposed drugs can improve the efficacy of treatment, and structure-based drug design can be employed to specifically target SARS-CoV-2. This review discusses therapeutic strategies using promising antiviral agents against SARS-CoV-2. In addition, structural characterization of potentially therapeutic viral or host cellular targets associated with COVID-19 have been discussed to refine structure-based drug design strategies.


id: cord-277400-w7mvk3x4
title: Identification of Capsid/Coat Related Protein Folds and Their Utility for Virus Classification
author: Nasir, Arshan
date: 2017-03-10
url: https://doi.org/10.3389/fmicb.2017.00380
doi: 10.3389/fmicb.2017.00380
abstract:
  The viral supergroup includes the entire collection of known and unknown viruses that roam our planet and infect life forms. The supergroup is remarkably diverse both in its genetics and morphology and has historically remained difficult to study and classify. The accumulation of protein structure data in the past few years now provides an excellent opportunity to re-examine the classification and evolution of viruses. Here we scan completely sequenced viral proteomes from all genome types and identify protein folds involved in the formation of viral capsids and virion architectures. Viruses encoding similar capsid/coat related folds were pooled into lineages, after benchmarking against published literature. Remarkably, the in silico exercise reproduced all previously described members of known structure-based viral lineages, along with several proposals for new additions, suggesting it could be a useful supplement to experimental approaches and to aid qualitative assessment of viral diversity in metagenome samples.


id: cord-277731-thazunob
title: Biosurfactants: A Covid-19 Perspective
author: Smith, Matthew L.
date: 2020-06-09
url: https://doi.org/10.3389/fmicb.2020.01341
doi: 10.3389/fmicb.2020.01341
abstract:
  The recent outbreak in severe acute respiratory syndrome – coronavirus-2 (SARS-CoV-2) has demonstrated the complete inability of nations across the world to cope with the pressures of a global pandemic, especially one in which the only current feasible treatments are those which deal with the symptoms alone and not the viral cause. As the death toll rises, scientists begin to fall toward new avenues of research, with novelty showing itself to be an incredible and so far, underrated resource. In this case, the use of biosurfactants in dealing with this pandemic justifies extensive study with their potential applications being in the prevention of viral spread; dealing with the symptoms that develop after the incubation period; directly targeting viral infected cells and preventing the spread of the virus throughout the host, all in addition to also acting as potential drug delivery systems and cleaning agents. This extensive avenue of biosurfactants owes to the simplicity in their amphiphilic structure which permits them to interact directly with the lipid membrane of the coronavirus, in a way which wouldn't be of significant threat to the host. Although it could possibly interact and affect the virus, it could also affect human internal organs/cells by interacting with lipid membrane, if (biosurfactant is) ingested, and it still needs further studies in human models. The structure of the coronavirus, in this case SARS-CoV-2, is detrimentally dependent on the integrity of its lipid membrane which encloses its vital proteins and RNA. Biosurfactants possess the innate ability to threaten this membrane, a result of their own hydrophobic domains across their amphiphilic structure. With biosurfactants additionally being both natural and sustainable, while also possessing a remarkably low cytotoxicity, it is of no doubt that they are going to be of increasing significance in dealing with the current pandemic.


id: cord-278540-gy65bvot
title: Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome
author: Chen, I-Yin
date: 2019-01-29
url: https://www.ncbi.nlm.nih.gov/pubmed/30761102/
doi: 10.3389/fmicb.2019.00050
abstract:
  Nod-like receptor family, pyrin domain-containing 3 (NLRP3) regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus (EMCV) 2B proteins stimulate IL-1β secretion following activation of the NLRP3 inflammasome. However, the mechanism by which severe acute respiratory syndrome coronavirus (SARS-CoV) activates the NLRP3 inflammasome remains unknown. Here, we provide direct evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages. SARS-CoV 3a was sufficient to cause the NLRP3 inflammasome activation. The ion channel activity of the 3a protein was essential for 3a-mediated IL-1β secretion. While cells uninfected or infected with a lentivirus expressing a 3a protein defective in ion channel activity expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells infected with a lentivirus expressing the 3a protein. K(+) efflux and mitochondrial reactive oxygen species were important for SARS-CoV 3a-induced NLRP3 inflammasome activation. These results highlight the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP3 inflammasome activation.


id: cord-281836-j1r771nq
author: Hernando-Amado, Sara
date: 2020-08-28
url: https://www.ncbi.nlm.nih.gov/pubmed/32983000/
doi: 10.3389/fmicb.2020.01914
title:
  Antibiotic Resistance: Moving From Individual Health Norms to Social Norms in One Health and Global Health

abstract:
  Antibiotic resistance is a problem for human health, and consequently, its study had been traditionally focused toward its impact for the success of treating human infections in individual patients (individual health). Nevertheless, antibiotic-resistant bacteria and antibiotic resistance genes are not confined only to the infected patients. It is now generally accepted that the problem goes beyond humans, hospitals, or long-term facility settings and that it should be considered simultaneously in human-connected animals, farms, food, water, and natural ecosystems. In this regard, the health of humans, animals, and local antibiotic-resistance–polluted environments should influence the health of the whole interconnected local ecosystem (One Health). In addition, antibiotic resistance is also a global problem; any resistant microorganism (and its antibiotic resistance genes) could be distributed worldwide. Consequently, antibiotic resistance is a pandemic that requires Global Health solutions. Social norms, imposing individual and group behavior that favor global human health and in accordance with the increasingly collective awareness of the lack of human alienation from nature, will positively influence these solutions. In this regard, the problem of antibiotic resistance should be understood within the framework of socioeconomic and ecological efforts to ensure the sustainability of human development and the associated human–natural ecosystem interactions.


id: cord-282305-l5r67gte
author: Zhang, Xuejiao
date: 2019-08-13
url: https://doi.org/10.3389/fmicb.2019.01829
doi: 10.3389/fmicb.2019.01829
title:
  Crystal Structure of Refolding Fusion Core of Lassa Virus GP2 and Design of Lassa Virus Fusion Inhibitors

abstract:
  The envelope glycoproteins GP1 and GP2 of Lassa virus (LASV) bind to the host cell receptors to mediate viral infection. So far, no approved vaccines and specific treatment options against LASV exist. To develop specific fusion inhibitors against LASV, we solved the crystal structure of the post-fusion 6 helix bundle (6-HB) formed by two heptad repeat domains (HR1 and HR2) of GP2. This fusion core contains a parallel trimeric coiled-coil of three HR1 helices, around which three HR2 helices are entwined in an antiparallel manner. Various hydrophobic and charged interactions form between HR1 and HR2 domains to stabilize the overall conformation of GP2 fusion core. Based on the structure, we designed several peptides spanning the HR2 domain and tested their antiviral activities. We found that the longer HR2 peptides were effective in inhibiting LASV GPC protein-mediated cell–cell fusion under low pH condition. These results not only suggest that LASV infects the target cell mainly through endocytosis, including micropinocytosis, and membrane fusion at low pH, but also provide an important basis for rational design of LASV fusion inhibitors.


id: cord-282797-thywse7g
title: Engineered Bacteriophage T7 as a Potent Anticancer Agent in vivo
author: Hwang, Yoon Jung
date: 2020-09-24
url: https://doi.org/10.3389/fmicb.2020.491001
doi: 10.3389/fmicb.2020.491001
abstract:
  Oncolytic viruses (OVs) induce antitumor effect by both direct lysis of target cells and eliciting immunogenic response to the virus and ultimately to the target cells. These viruses are usually natural human pathogens. Bacteriophages are natural pathogens of bacteria that do not infect human and have greater advantages in safety, manipulation, and production over human viruses. We constructed an engineered bacteriophage T7 displaying a peptide, which targets murine melanoma cells and harbors a mammalian expression cassette of the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) in viral genomic DNA. The engineered phage was successfully transduced to B16F10 melanoma cells both in vitro and in vivo. GM-CSF was expressed from the transduced phage DNA. All mice treated with the phage intravenously survived for 25 days until the end of experiment, while only 40% of those not treated survived. During the 16 days of phage treatment, phage T7 displaying homing peptide and expressing GM-CSF inhibited tumor growth by 72% compared to the untreated control. Serum cytokine levels of IL-1α, TNF-α, and GM-CSF were seen to increase during the treatment. Immunohistochemical analysis of tumor tissue revealed infiltration by macrophages, dendritic cells (DCs), and CD8(+) T cells. Migration of murine macrophages to bacteriophages was also observed in in vitro transwell assays in both time- and dose-dependent manners. Taken together, the recombinant bacteriophage T7 efficiently inhibited tumor growth by changing the tumor microenvironment and recruiting anti-tumor immune cells.


id: cord-284889-hth8nf5b
title: Molecular epidemiology of respiratory viruses in virus-induced asthma
author: Tsukagoshi, Hiroyuki
date: 2013-09-12
url: https://doi.org/10.3389/fmicb.2013.00278
doi: 10.3389/fmicb.2013.00278
abstract:
  Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.


id: cord-285868-fz5utxss
title: ER stress, autophagy, and RNA viruses
author: Jheng, Jia-Rong
date: 2014-08-05
url: https://www.ncbi.nlm.nih.gov/pubmed/25140166/
doi: 10.3389/fmicb.2014.00388
abstract:
  Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment.


id: cord-286779-si3qml42
author: Li, Hai-yan
date: 2020-06-04
url: https://www.ncbi.nlm.nih.gov/pubmed/32582042/
doi: 10.3389/fmicb.2020.00897
title:
  Modulation of Gut Microbiota, Short-Chain Fatty Acid Production, and Inflammatory Cytokine Expression in the Cecum of Porcine Deltacoronavirus-Infected Chicks

abstract:
  Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea and induces proinflammatory cytokine responses in piglets. Our previous research showed that the specific-pathogen-free (SPF) chicks exhibited mild diarrhea and low fecal viral shedding, along with cecum lesions after PDCoV infection. Disturbances in the homeostasis of the gut microbiota have been associated with various diseases. We aimed to explore the effects of PDCoV infection on chick gut microbiota, short-chain fatty acid (SCFAs) production, and inflammatory cytokine expression in chicks, and also to investigate the relationship between gut microbiota and SCFAs or inflammatory cytokine expression of the PDCoV-infected chicks. Results obtained using 16S rRNA sequencing showed that infection with PDCoV strain HNZK-02 significantly altered the composition of chick gut microbiota, with the reduced abundance of Eisenbergiella and Anaerotruncus genera at 5 days post-inoculation (dpi) (P < 0.05), and an increased abundance of Alistipes genus at 17 dpi (P < 0.05). The production of SCFAs in the cecum of PDCoV HNZK-02–infected chicks, including acetic acid, propionic acid, and butyric acid, decreased in all cases. The expression of inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-10) was increased in the cecum tissue and serum of the PDCoV HNZK-02–infected chicks when detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Further analysis showed significant correlation between bacterial genera and SCFAs or inflammatory cytokines expression in cecum of the PDCoV infected chicks. These findings might provide new insight into the pathology and physiology of PDCoV in chicks.


id: cord-289623-7oc1ykds
author: Gendy, Sherif
date: 2020-08-20
url: https://doi.org/10.3389/fmicb.2020.01923
doi: 10.3389/fmicb.2020.01923
title:
  Is Long-Term Heavy Metal Exposure Driving Carriage of Antibiotic Resistance in Environmental Opportunistic Pathogens: A Comprehensive Phenomic and Genomic Assessment Using Serratia sp. SRS-8-S-2018

abstract:
  The carriage of both, heavy metal and antibiotic resistance appears to be a common trait in bacterial communities native to long-term contaminated habitats, including the Savannah River Site (SRS). There is widespread soil contamination at the SRS; a United States Department of Energy (DOE) facility with long-term contamination from past industrial and nuclear weapons production activities. To further evaluate the genomic and metabolic traits that underpin metal and antibiotic resistance, a robust mercury (Hg) and uranium (U)-resistant strain- SRS-8-S-2018, was isolated. Minimum inhibitory concentration of this strain revealed resistance to Hg (10 μg/ml) and U (5 mM), the two main heavy metal contaminants at the SRS. Metabolic assessment of strain SRS-8-S-2018 using Biolog metabolic fingerprinting analysis revealed preference for carbohydrate utilization followed by polymers, amino acids, carboxy acids, and esters; this physiological activity diminished when Hg stress was provided at 1 and 3 μg/ml and completely ceased at 5 μg/ml Hg, indicating that continued release of Hg will have negative metabolic impacts to even those microorganisms that possess high resistance ability. Development of antibiotic resistance in strain SRS-8-S-2018 was evaluated at a functional level using phenomics, which confirmed broad resistance against 70.8% of the 48 antibiotics tested. Evolutionary and adaptive traits of strain SRS-8-S-2018 were further assessed using genomics, which revealed the strain to taxonomically affiliate with Serratia marcescens species, possessing a genome size of 5,323,630 bp, 5,261 proteins (CDS), 55 genes for transfer RNA (tRNA), and an average G + C content of 59.48. Comparative genomics with closest taxonomic relatives revealed 360 distinct genes in SRS-8-S-2018, with multiple functions related to both, antibiotic and heavy metal resistance, which likely facilitates the strain’s survival in a metalliferous soil habitat. Comparisons drawn between the environmentally isolated Serratia SRS-8-S-2018 with 31 other strains revealed a closer functional association with medically relevant isolates suggesting that propensity of environmental Serratia isolates in acquiring virulence traits, as a function of long-term exposure to heavy metals, which is facilitating development, recruitment and proliferation of not only metal resistant genes (MRGs) but antibiotic resistant genes (ARGs), which can potentially trigger future bacterial pathogen outbreaks emanating from contaminated environmental habitats.


id: cord-290505-omszep7u
title: Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients
author: Pochon, Cécile
date: 2019-01-09
url: https://www.ncbi.nlm.nih.gov/pubmed/30687278/
doi: 10.3389/fmicb.2018.03294
abstract:
  Highly immunocompromised pediatric and adult hematopoietic cell transplant (HCT) recipients frequently experience respiratory infections caused by viruses that are less virulent in immunocompetent individuals. Most of these infections, with the exception of rhinovirus as well as adenovirus and parainfluenza virus in tropical areas, are seasonal variable and occur before and after HCT. Infectious disease management includes sampling of respiratory specimens from nasopharyngeal washes or swabs as well as sputum and tracheal or tracheobronchial lavages. These are subjected to improved diagnostic tools including multiplex PCR assays that are routinely used allowing for expedient detection of all respiratory viruses. Disease progression along with high mortality is frequently associated with respiratory syncytial virus, parainfluenza virus, influenza virus, and metapneumovirus infections. In this review, we discuss clinical findings and the appropriate use of diagnostic measures. Additionally, we also discuss treatment options and suggest new drug formulations that might prove useful in treating respiratory viral infections. Finally, we shed light on the role of the state of immune reconstitution and on the use of immunosuppressive drugs on the outcome of infection.


id: cord-291295-7og5umiq
author: Xin, Shuyu
date: 2019-12-13
url: https://doi.org/10.3389/fmicb.2019.02879
doi: 10.3389/fmicb.2019.02879
title:
  Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

abstract:
  Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Cyclophilin A (CYPA) is upregulated in EBV-associated nasopharyngeal carcinoma (NPC) with unknown roles. In the present approach, cytosolic CYPA was found to be bound with EBNA1 into the nucleus. The amino acid 376-459 of the EBNA1 domain was important for the binding. CYPA depletion attenuated and ectopic CYPA expression improved EBNA1 expression in EBV-positive cells. The loss of viral copy number was also accelerated by CYPA consumption in daughter cells during culture passages. Mechanistically, CYPA mediated the connection of EBNA1 with oriP (origin of EBV DNA replication) and subsequent oriP transcription, which is a key step for the initiation of EBV genome replication. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitin-specific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. The PPIase activity of CYPA was required for the promotion of oriP transcription and antagonism with USP7. The results revealed a strategy that EBV recruited a host factor to counteract the host defense, thus facilitating its own latent genome replication. This study provides a new insight into EBV pathogenesis and potential virus-targeted therapeutics in EBV-associated NPC, in which CYPA is upregulated at all stages.


id: cord-293675-bojfc3q0
author: Han, Yelin
date: 2019-08-14
url: https://www.ncbi.nlm.nih.gov/pubmed/31474969/
doi: 10.3389/fmicb.2019.01900
title:
  Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases

abstract:
  Outbreaks of severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome in 2012 and fatal swine acute diarrhea syndrome in 2017 caused serious infectious diseases in humans and in livestock, resulting in serious public health threats and huge economic losses. All such coronaviruses (CoVs) were confirmed to originate from bats. To continuously monitor the epidemic-related CoVs in bats, virome analysis was used to classify CoVs from 831 bats of 15 species in Yunnan, Guangxi, and Sichuan Provinces between August 2016 and May 2017. We identified 11 CoV strains from 22 individual samples of four bat species. Identification of four alpha-CoVs from Scotophilus kuhlii in Guangxi, which was closely related to a previously reported bat CoV and porcine epidemic diarrhea virus (PEDV), revealed a bat-swine lineage under the genus Alphacoronavirus. A recombinant CoV showed that the PEDV probably originated from the CoV of S. kuhlii. Another alpha-CoV, α-YN2018, from Rhinolophus affinis in Yunnan, suggested that this alpha-CoV lineage had multiple host origins, and α-YN2018 had recombined with CoVs of other bat species over time. We identified five SARS-related CoVs (SARSr-CoVs) in Rhinolophus bats from Sichuan and Yunnan and confirmed that angiotensin-converting enzyme 2 usable SARSr-CoVs were continuously circulating in Rhinolophus spp. in Yunnan. The other beta-CoV, strain β-GX2018, found in Cynopterus sphinx of Guangxi, represented an independently evolved lineage different from known CoVs of Rousettus and Eonycteris bats. The identification of diverse CoVs here provides new genetic data for understanding the distribution and source of pathogenic CoVs in China.


id: cord-295240-76ee00i0
author: Kruchten, Anne E.
date: 2020-09-10
url: https://www.ncbi.nlm.nih.gov/pubmed/33013816/
doi: 10.3389/fmicb.2020.578600
title:
  A Curricular Bioinformatics Approach to Teaching Undergraduates to Analyze Metagenomic Datasets Using R

abstract:
  Biologists with bioinformatic skills will be better prepared for the job market, but relatively few biology programs require bioinformatics courses. Inclusion in the curriculum may be hindered by several barriers, including lack of faculty expertise, student resistance to computational work, and few examples in the pedagogical literature. An 8-week wet-lab and in silico research experience for undergraduates was implemented. Students performed DNA purification and metagenomics analysis to compare the diversity and abundance of microbes in two samples. Students sampled snow from sites in northern Minnesota and purified genomic DNA from the microbes, followed by metagenomic analysis. Students used an existing metagenomic dataset to practice analysis skills, including comparing the use of Excel versus R for analysis and visualization of a large dataset. Upon receipt of the snow data, students applied their recently acquired skills to their new dataset and reported their results via a poster. Several outcomes were achieved as a result of this module. First, YouTube videos demonstrating hands-on metagenomics and R techniques were used as professional development for faculty, leading to broadened research capabilities and comfort with bioinformatics. Second, students were introduced to computational skills in a manner that was intentional, with time for both introduction and reinforcement of skills. Finally, the module was effectively included in a biology curriculum because it could function as either a stand-alone course or a module within another course such as microbiology. This module, developed with Course-based Undergraduate Research Experience guidelines in mind, introduces students and faculty to bioinformatics in biology research.


id: cord-296495-9v0sq8k6
title: Infection with and Carriage of Mycoplasma pneumoniae in Children
author: Meyer Sauteur, Patrick M.
date: 2016-03-23
txt: ./txt/cord-296495-9v0sq8k6.txt
cache: ./cache/cord-296495-9v0sq8k6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27047456/
doi: 10.3389/fmicb.2016.00329
summary:
  Mycoplasma pneumoniae causes both upper and lower respiratory tract infections, with community-acquired pneumonia (CAP) as the major burden of disease. pneumoniae infections were first reported in 1960 when 16% of 110 children with lower respiratory tract disease were tested positive by a fourfold rise in antibody titers against the Eaton agent (Chanock et al., 1960) . This study described 20 patients with CAP, of which 19 were children 4-15 years of age, diagnosed by a significant rise in antibody titers against M. Emergence of macrolide-resistant strains during an outbreak of Mycoplasma pneumoniae infections in children Results of molecular detection of Mycoplasma pneumoniae among patients with acute respiratory infection and in their household contacts reveals children as human reservoirs Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections

abstract:
  “Atypical” pneumonia was described as a distinct and mild form of community-acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered and recognized as its cause. M. pneumoniae is detected in CAP patients most frequently among school-aged children from 5 to 15 years of age, with a decline after adolescence and tapering off in adulthood. Detection rates by polymerase chain reaction (PCR) or serology in children with CAP admitted to the hospital amount 4–39%. Although the infection is generally mild and self-limiting, patients of every age can develop severe or extrapulmonary disease. Recent studies indicate that high rates of healthy children carry M. pneumoniae in the upper respiratory tract and that current diagnostic PCR or serology cannot discriminate between M. pneumoniae infection and carriage. Further, symptoms and radiologic features are not specific for M. pneumoniae infection. Thus, patients may be unnecessarily treated with antimicrobials against M. pneumoniae. Macrolides are the first-line antibiotics for this entity in children younger than 8 years of age. Overall macrolides are extensively used worldwide, and this has led to the emergence of macrolide-resistant M. pneumoniae, which may be associated with severe clinical features and more extrapulmonary complications. This review focuses on the characteristics of M. pneumoniae infections in children, and exemplifies that simple clinical decision rules may help identifying children at high risk for CAP due to M. pneumoniae. This may aid physicians in prescribing appropriate first-line antibiotics, since current diagnostic tests for M. pneumoniae infection are not reliably predictive.


id: cord-297662-slmlhqnb
title: Dengue Virus Glycosylation: What Do We Know?
author: Yap, Sally S. L.
date: 2017-07-25
txt: ./txt/cord-297662-slmlhqnb.txt
cache: ./cache/cord-297662-slmlhqnb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2017.01415
doi: 10.3389/fmicb.2017.01415
summary:
  In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis. Since high mannose binding DC-SIGN interacts only with N67 glycans on the viral surface (Pokidysheva et al., 2006) and N153-glycan is dispensable for virus production in mosquito and mammalian cells (Bryant et al., 2007) , this suggests that N153 glycans may serve a distinct function from N67 glycans in DEN pathogenesis possibly via interaction with an unknown fucose binder or act as a viral glycan shield. Finally, N153 deglycosylated (N153 − ) DENV mutant displayed reduced infectivity (10-fold lower) in both mammalian and mosquito cells compared to WT, possibly due to impaired virus entry process (Lee et al., 1997; Hacker et al., 2009) , whereby loss of the N153-glycan affected the conformational stability of E proteins and led to premature exposure of the fusion peptide (Yoshii et al., 2013) . N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement

abstract:
  In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E) and non-structural protein 1 (NS1) are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.


id: cord-298032-3zlu8g8y
title: Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds
author: Nan, Yuchen
date: 2018-04-20
url: https://doi.org/10.3389/fmicb.2018.00750
doi: 10.3389/fmicb.2018.00750
abstract:
  Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.


id: cord-298233-qqhgmqrg
title: Molecular Biology and Infection of Hepatitis E Virus
author: Nan, Yuchen
date: 2016-09-07
txt: ./txt/cord-298233-qqhgmqrg.txt
cache: ./cache/cord-298233-qqhgmqrg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2016.01419
doi: 10.3389/fmicb.2016.01419
summary:
  More interestingly, a remarkable HEV strain Kernow-C1, which was originally isolated from an HIV-positive patient with chronic HEV infection, contains an insertion of a 174 nt gene fragment of human ribosomal protein S17 in the Pro region (Shukla et al., 2011) . Furthermore, other studies indicate that the expression of viral macro domain in liver cells inhibits apoptosis since it is functionally related to poly(ADP-ribose) polymerase-1 (PARP-1; Allen et al., 2003; Chen et al., 2009) , suggesting a role in apoptosis during viral infection. Identification of critical residues in hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins ORF3 protein of hepatitis E virus is not required for replication, virion assembly, or infection of hepatoma cells in vitro A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells The ORF2 protein of hepatitis E virus binds the 5 region of viral RNA ORF3 protein of hepatitis E virus is essential for virion release from infected cells

abstract:
  Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.


id: cord-298240-vcph52gn
title: The unfolded protein response in virus infections
author: Chan, Shiu-Wan
date: 2014-09-30
txt: ./txt/cord-298240-vcph52gn.txt
cache: ./cache/cord-298240-vcph52gn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25324837/
doi: 10.3389/fmicb.2014.00518
abstract: nan
summary:
  This research topic collated a number of review articles and original research article, in an attempt to highlight how viruses interact with the host UPR in the establishment of acute, chronic and latent infections. The relationship between virus and UPR and its associated autophagy is being addressed in three reviews focusing on RNA viruses, as their life cycles are closely associated with the ER (Blazquez et al., 2014; Fung and Liu, 2014; Jheng et al., 2014) . An important question remains as to whether UPR represents a new tool for sensing viruses or select UPR molecules are merely being co-opted in "microbial stress response." This is being addressed in Judith Smith''s review, in which she provides a critique on the intersection of the UPR with the inflammatory pathways and innate immunity and offers an insight into UPR-PRR synergy as an evolutionary adaptation to ensure specificity of anti-viral responses (Smith, 2014) .


id: cord-300379-db79kb5c
title: Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid
author: Park, Jun-Gyu
date: 2019-04-12
url: https://www.ncbi.nlm.nih.gov/pubmed/31031722/
doi: 10.3389/fmicb.2019.00718
abstract:
  Zika virus (ZIKV) is one of the recently emerging vector-borne viruses in humans and is responsible for severe congenital abnormalities such as microcephaly in the Western Hemisphere. Currently, only a few vaccine candidates and therapeutic drugs are being developed for the treatment of ZIKV infections, and as of yet none are commercially available. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antimicrobial and antiviral activity. In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC(50)) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC(50)) > 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication with similar IC(50). Importantly, the inhibitory effect of ATA on ZIKV infection was effective against strains of the African and Asian/American lineages, indicating that this inhibitory effect was not strain dependent. Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a potential anti-ZIKV therapy for future clinical evaluation.


id: cord-302854-buzyani0
author: Prabakaran, Ponraj
date: 2012-08-02
url: https://doi.org/10.3389/fmicb.2012.00277
doi: 10.3389/fmicb.2012.00277
title:
  Origin, diversity, and maturation of human antiviral antibodies analyzed by high-throughput sequencing

abstract:
  Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS coronavirus (SARS CoV), and Hendra and Nipah viruses (henipaviruses). Although broadly neutralizing antibodies (bnAbs) against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large naïve library of human IgM antibodies which had been used for selecting antibodies against SARS CoV receptor-binding domain (RBD), and soluble G proteins (sG) of henipaviruses. We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity, and a lower extent of somatic mutation. In this study, we identified antibody maturation intermediates that are related to bnAbs against the HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics.


id: cord-302928-nnly9ju8
author: Adachi, Akio
date: 2020-03-18
txt: ./txt/cord-302928-nnly9ju8.txt
cache: ./cache/cord-302928-nnly9ju8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32256480/
doi: 10.3389/fmicb.2020.00431
abstract: nan
summary:
  Most cited articles and most viewed RTs in the human/animal virus field of the section (top 5, as of February 3, 2020) are as follows, respectively: articles, "Epidemiological aspects and world distribution of HTLV-1 infection" (Gessain and Cassar, 2012) , "Pathology of asthma" (Kudo et al., 2013) , "Challenges and opportunities in estimating viral genetic diversity from next-generation sequencing data" (Beerenwinkel et al., 2012) , "ER stress, autophagy, and RNA viruses" (Jheng et al., 2014) , and "Zika virus: the latest newcomer" (Saiz et al., 2016) ; RTs, "Highly mutable animal RNA viruses: adaptation and evolution" , "Virus discovery by metagenomics: the (im)possibilities" (Dutilh et al., 2017) , "Zika virus research" (Bueno-Marí et al., 2018), "Pathophysiology and epidemiology of virus-induced asthma" (Kimura and Ryo, 2014) , and "Forefront studies on HTLV-1 oncogenesis" (Mahieux and Watanabe, 2013) .

title:
  Grand Challenge in Human/Animal Virology: Unseen, Smallest Replicative Entities Shape the Whole Globe


id: cord-305973-i3raopi6
author: Perley, Casey C.
date: 2020-05-07
txt: ./txt/cord-305973-i3raopi6.txt
cache: ./cache/cord-305973-i3raopi6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32508764/
doi: 10.3389/fmicb.2020.00832
summary:
  These data demonstrate that DNA vaccines combined with the TcB-based manufacturing platform can be used to rapidly produce potent, human, polyclonal, escape-resistant anti-HTNV, and anti-PUUV neutralizing antibodies that are protective in animal models. Here, we demonstrate that it is possible to combine DNA vaccine technology with the TcB platform to produce potent human polyclonal IgG for use as a pre-or post-exposure prophylactic for HFRS caused by HTNV and PUUV infection. Previous experiments to produce anti-ANDV and anti-SNV TcB human IgG have demonstrated that including an SAB-adj-1 adjuvant at the injection sight increased immunogenicity of the ANDV and SNV DNA vaccines resulting in higher titer virusspecific neutralizing antibodies (Hooper et al., 2014a) . To determine the dose of SAB-159 required to protect against infection, hamsters were administered decreasing concentrations of neutralizing antibody ranging from 12.23 mg/kg to 0.39 mg/kg SAB-159 subcutaneously 1 day prior to a 10 PFU HTNV challenge.

title:
  Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models

abstract:
  We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala virus (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics. The technology involves hyperimmunization of transchomosomic bovines (TcB) engineered to express human polyclonal IgG antibodies with HTNV and PUUV DNA vaccines encoding G(n)G(c) glycoproteins. For the anti-HTNV product, TcB was hyperimmunized with HTNV DNA plus adjuvant or HTNV DNA formulated using lipid nanoparticles (LNP). The LNP-formulated vaccine yielded fivefold higher neutralizing antibody titers using 10-fold less DNA. Human IgG purified from the LNP-formulated animal (SAB-159), had anti-HTNV neutralizing antibody titers >100,000. SAB-159 was capable of neutralizing pseudovirions with monoclonal antibody escape mutations in G(n) and G(c) demonstrating neutralization escape resistance. SAB-159 protected hamsters from HTNV infection when administered pre- or post-exposure, and limited HTNV infection in a marmoset model. An LNP-formulated PUUV DNA vaccine generated purified anti-PUUV IgG, SAB-159P, with a neutralizing antibody titer >600,000. As little as 0.33 mg/kg of SAB-159P protected hamsters against PUUV infection for pre-exposure and 10 mg/kg SAB-159P protected PUUV-infected hamsters post-exposure. These data demonstrate that DNA vaccines combined with the TcB-based manufacturing platform can be used to rapidly produce potent, human, polyclonal, escape-resistant anti-HTNV, and anti-PUUV neutralizing antibodies that are protective in animal models.


id: cord-310392-fmobf1f1
title: SARS-CoV-2 Genome Analysis of Japanese Travelers in Nile River Cruise
author: Sekizuka, Tsuyoshi
date: 2020-06-05
url: https://doi.org/10.3389/fmicb.2020.01316
doi: 10.3389/fmicb.2020.01316
abstract:
  Japan has reported 26 cases of coronavirus disease 2019 (COVID-19) linked to cruise tours on the River Nile in Egypt between March 5 and 15, 2020. Here, we characterized the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome of isolates from 10 travelers who returned from Egypt and from patients possibly associated with these travelers. We performed haplotype network analysis of SARS-CoV-2 isolates using genome-wide single-nucleotide variations. Our analysis identified two potential Egypt-related clusters from these imported cases, and these clusters were related to globally detected viruses in different countries.


id: cord-312336-784izxqd
author: Fouret, Julien
date: 2020-07-29
url: https://doi.org/10.3389/fmicb.2020.01807
doi: 10.3389/fmicb.2020.01807
title:
  Sequencing the Genome of Indian Flying Fox, Natural Reservoir of Nipah Virus, Using Hybrid Assembly and Conservative Secondary Scaffolding

abstract:
  Indian fruit bats, flying fox Pteropus medius was identified as an asymptomatic natural host of recently emerged Nipah virus, which is known to induce a severe infectious disease in humans. The absence of P. medius genome sequence presents an important obstacle for further studies of virus–host interactions and better understanding of mechanisms of zoonotic viral emergence. Generation of the high-quality genome sequence is often linked to a considerable effort associated to elevated costs. Although secondary scaffolding methods have reduced sequencing expenses, they imply the development of new tools for the integration of different data sources to achieve more reliable sequencing results. We initially sequenced the P. medius genome using the combination of Illumina paired-end and Nanopore sequencing, with a depth of 57.4x and 6.1x, respectively. Then, we introduced the novel scaff2link software to integrate multiple sources of information for secondary scaffolding, allowing to remove the association with discordant information among two sources. Different quality metrics were next produced to validate the benefits from secondary scaffolding. The P. medius genome, assembled by this method, has a length of 1,985 Mb and consists of 33,613 contigs and 16,113 scaffolds with an NG50 of 19 Mb. At least 22.5% of the assembled sequences is covered by interspersed repeats already described in other species and 19,823 coding genes are annotated. Phylogenetic analysis demonstrated the clustering of P. medius genome with two other Pteropus bat species, P. alecto and P. vampyrus, for which genome sequences are currently available. SARS-CoV entry receptor ACE2 sequence of P. medius was 82.7% identical with ACE2 of Rhinolophus sinicus bats, thought to be the natural host of SARS-CoV. Altogether, our results confirm that a lower depth of sequencing is enough to obtain a valuable genome sequence, using secondary scaffolding approaches and demonstrate the benefits of the scaff2link application. The genome sequence is now available to the scientific community to (i) proceed with further genomic analysis of P. medius, (ii) to characterize the underlying mechanism allowing Nipah virus maintenance and perpetuation in its bat host, and (iii) to monitor their evolutionary pathways toward a better understanding of bats’ ability to control viral infections.


id: cord-314567-purplsjn
title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells
author: Fernández-Ponce, Cecilia
date: 2018-01-04
url: https://www.ncbi.nlm.nih.gov/pubmed/29354102/
doi: 10.3389/fmicb.2017.02595
abstract:
  Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4(+) T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells. In order to investigate the intracellular localization of Hepatitis C virus core protein, we have used a lentiviral system to transduce Jurkat T cells and subsequently localize the protein using immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis C virus core protein mostly localizes in the nucleus and specifically in the nucleolus. In addition, we performed pull-down assays combined with Mass Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus core in Jurkat T cells. We found proteins such as NOLC1, PP1γ, ILF3, and C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4(+) T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. Thus, in the current work, we show the ultrastructural localization of Hepatitis C virus core and the first profile of HCV core associated proteins in T cells, and we discuss the functions and interconnections of these proteins in molecular networks where relevant biological modifications have been described upon the expression of Hepatitis C virus core protein. Thereby, the current work constitutes a necessary step toward understanding the mechanisms underlying HCV core mediated alterations that had been described in relevant biological processes in CD4(+) T cells.


id: cord-315834-ashjw2xs
title: Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score
author: Guo, Lingxi
date: 2019-12-03
txt: ./txt/cord-315834-ashjw2xs.txt
cache: ./cache/cord-315834-ashjw2xs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31849894/
doi: 10.3389/fmicb.2019.02752
summary:
  title: Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score OBJECTIVE: The aim of this study was to further clarify clinical characteristics and predict mortality risk among patients with viral pneumonia. CONCLUSION: Here, we designed an easy-to-use clinically predictive tool for assessing 90-day mortality risk of viral pneumonia. Influenza and other respiratory viruses are common reasons of acute pneumonia which can result in significant morbidity or mortality in the setting of high-risk factors such as extremes of age, pregnancy, obesity or chronic pre-existing conditions. Other reported risk factors for influenza pneumonia such as PO2/FiO2, lymphocyte count, and antigen-specific T cells are likewise useful in predicting mortality and deciding on appropriate management (Viasus et al., 2011; Shi et al., 2017) . In patients hospitalized with viral pneumonia, a simple prognostic tool was made for overall mortality which is useful for prediction several days after admission upon obtaining culture results.

abstract:
  OBJECTIVE: The aim of this study was to further clarify clinical characteristics and predict mortality risk among patients with viral pneumonia. METHODS: A total of 528 patients with viral pneumonia at RuiJin hospital in Shanghai from May 2015 to May 2019 were recruited. Multiplex real-time RT-PCR was used to detect respiratory viruses. Demographic information, comorbidities, routine laboratory examinations, immunological indexes, etiological detections, radiological images and treatment were collected on admission. RESULTS: 76 (14.4%) patients died within 90 days in hospital. A predictive MuLBSTA score was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included multilobular infiltrates (OR = 5.20, 95% CI 1.41–12.52, p = 0.010; 5 points), lymphocyte ≤ 0.8(∗)10(9)/L (OR = 4.53, 95% CI 2.55–8.05, p < 0.001; 4 points), bacterial coinfection (OR = 3.71, 95% CI 2.11–6.51, p < 0.001; 4 points), acute-smoker (OR = 3.19, 95% CI 1.34–6.26, p = 0.001; 3 points), quit-smoker (OR = 2.18, 95% CI 0.99–4.82, p = 0.054; 2 points), hypertension (OR = 2.39, 95% CI 1.55–4.26, p = 0.003; 2 points) and age ≥60 years (OR = 2.14, 95% CI 1.04–4.39, p = 0.038; 2 points). 12 points was used as a cut-off value for mortality risk stratification. This model showed sensitivity of 0.776, specificity of 0.778 and a better predictive ability than CURB-65 (AUROC = 0.773 vs. 0.717, p < 0.001). CONCLUSION: Here, we designed an easy-to-use clinically predictive tool for assessing 90-day mortality risk of viral pneumonia. It can accurately stratify hospitalized patients with viral pneumonia into relevant risk categories and could provide guidance to make further clinical decisions.


id: cord-316176-rqc6kvsl
author: Crémet, Lise
date: 2020-08-25
txt: ./txt/cord-316176-rqc6kvsl.txt
cache: ./cache/cord-316176-rqc6kvsl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2020.02080
doi: 10.3389/fmicb.2020.02080
summary:
  The FilmArray(®) Pneumonia plus Panel (FAPP) is a new multiplex molecular test for hospital-acquired pneumonia (HAP), which can rapidly detect 18 bacteria, 9 viruses, and 7 resistance genes. The FilmArray R Pneumonia plus Panel (FAPP) is a new panel for HAP, which offers potential advantage to detect and quantify in a single test, 27 respiratory pathogens (18 bacteria, 9 viruses) and 7 antibiotic resistance genes. At the time of HAP diagnosis, FAPP yielded positive results with significant levels (i.e., ≥ 10 4 bin in BAL and ≥ 10 5 bin in ETA for semi-quantified bacteria) in 82/100 patients. In this study, this test was compared to routine microbiological methods using 237 prospectively collected BAL and ETA specimens obtained from 100 ICU patients at the time of suspected HAP and, if possible, at a later timepoint during follow-up.

title:
  Evaluation of the FilmArray(®) Pneumonia Plus Panel for Rapid Diagnosis of Hospital-Acquired Pneumonia in Intensive Care Unit Patients

abstract:
  The FilmArray(®) Pneumonia plus Panel (FAPP) is a new multiplex molecular test for hospital-acquired pneumonia (HAP), which can rapidly detect 18 bacteria, 9 viruses, and 7 resistance genes. We aimed to compare the diagnosis performance of FAPP with conventional testing in 100 intensive care unit (ICU) patients who required mechanical ventilation, with clinically suspected HAP. A total of 237 samples [76 bronchoalveolar lavages (BAL(DS)) and 82 endotracheal aspirates (ETA(DS)) obtained at HAP diagnosis, and 79 ETA obtained during follow-up (ETA(TT))], were analyzed independently by routine microbiology testing and FAPP. 58 patients had paired BAL(DS) and ETA(DS). The positivity thresholds of semi-quantified bacteria were 10(3)–10(4) CFUs/mL or 10(4) copies/mL for BAL, and 10(5) CFUs/mL or copies/mL for ETA. Respiratory commensals (H. influenzae, S. aureus, E. coli, S. pneumoniae) were the most common pathogens. Discordant results for bacterial identification were observed in 33/76 (43.4%) BAL(DS) and 36/82 (43.9%) ETA(DS), and in most cases, FAPP identified one supplemental bacteria (23/33 BAL(DS) and 21/36 ETA(DS)). An absence of growth, or polybacterial cultures, explained almost equally the majority of the non-detections in culture. No linear relationship was observed between bin and CFUs/mL variables. Concordant results between paired BAL(DS) and ETA(DS) were obtained in 46/58 (79.3%) patients with FAPP. One of the 17 resistance genes detected with FAPP (mecA/C and MREJ) was not confirmed by conventional testing. Overall, FAPP enhanced the positivity rate of diagnostic testing, with increased recognition of coinfections. Implementing this strategy may allow clinicians to make more timely and informed decisions.


id: cord-316537-f5rto51t
author: Loens, Katherine
date: 2016-03-31
url: https://www.ncbi.nlm.nih.gov/pubmed/27064893/
doi: 10.3389/fmicb.2016.00448
title:
  Mycoplasma pneumoniae: Current Knowledge on Nucleic Acid Amplification Techniques and Serological Diagnostics

abstract:
  Mycoplasma pneumoniae (M. pneumoniae) belongs to the class Mollicutes and has been recognized as a common cause of respiratory tract infections (RTIs), including community-acquired pneumonia (CAP), that occur worldwide and in all age groups. In addition, M. pneumoniae can simultaneously or sequentially lead to damage in the nervous system and has been associated with a wide variety of other acute and chronic diseases. During the past 10 years, the proportion of LRTI in children and adults, associated with M. pneumoniae infection has ranged from 0 to more than 50%. This variation is due to the age and the geographic location of the population examined but also due to the diagnostic methods used. The true role of M. pneumoniae in RTIs remains a challenge given the many limitations and lack of standardization of the applied diagnostic tool in most cases, with resultant wide variations in data from different studies. Correct and rapid diagnosis and/or management of M. pneumoniae infections is, however, critical to initiate appropriate antibiotic treatment and is nowadays usually done by PCR and/or serology. Several recent reviews, have summarized current methods for the detection and identification of M. pneumoniae. This review will therefore provide a look at the general principles, advantages, diagnostic value, and limitations of the most currently used detection techniques for the etiological diagnosis of a M. pneumoniae infection as they evolve from research to daily practice.


id: cord-317499-mxt7stat
author: Saraya, Takeshi
date: 2014-05-26
txt: ./txt/cord-317499-mxt7stat.txt
cache: ./cache/cord-317499-mxt7stat.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24904541/
doi: 10.3389/fmicb.2014.00226
summary:
  Table 1 shows the frequency of HRV infection in various adult respiratory diseases such as exacerbation of asthma (Nicholson et al., 1993; Atmar et al., 1998; Tan et al., 2003) , common cold (Makela et al., 1998; van Gageldonk-Lafeber et al., 2005) , exacerbation of COPD (Seemungal et al., 2001; Rohde et al., 2003; Tan et al., 2003; Beckham et al., 2005; Papi et al., 2006; Hutchinson et al., 2007; Ko et al., 2007; McManus et al., 2008; Kherad et al., 2010; Dimopoulos et al., 2012; Perotin et al., 2013) , community acquired pneumonia (Jennings et al., 2008; Johnstone et al., 2008; Johansson et al., 2010; Lieberman et al., 2010; Fry et al., 2011; Wootton et al., 2011; Luchsinger et al., 2013; Takahashi et al., 2013; Huijskens et al., 2014) , exacerbation of idiopathic pulmonary fibrosis (Wootton et al., 2011) , and asymptomatic infection (Fry et al., 2011) .

title:
  Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus

abstract:
  Viral respiratory infections may be associated with the virus-induced asthma in adults as well as children. Particularly, human rhinovirus is strongly suggested a major candidate for the associations of the virus-induced asthma. Thus, in this review, we reviewed and focused on the epidemiology, pathophysiology, and treatment of virus-induced asthma with special reference on human rhinovirus. Furthermore, we added our preliminary data regarding the clinical and virological findings in the present review.


id: cord-317595-siwzjeea
title: Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
author: Forni, Diego
date: 2018-05-01
txt: ./txt/cord-317595-siwzjeea.txt
cache: ./cache/cord-317595-siwzjeea.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29765366/
doi: 10.3389/fmicb.2018.00854
summary:
  Herein, we apply an evolutionary approach to shed light into HCV origin, to analyze its adaptation to human populations, and to verify if the emergence of drug-resistant variants is a result of positive selection. We used Single-Likelihood Ancestor Counting (SLAC) and fixed effects likelihood (FEL) (Kosakovsky Pond and Frost, 2005) to calculate the rates of nonsynonymous and synonymous changes at each site in the structural and in the non-structural region alignments (analyses were performed on alignments split on the basis of the recombination breakpoint detected by GARD). The observation that the positively selected sites are involved in HCV binding and infectivity suggests that hepaciviruses contributed to shape the genetic diversity of CD81 in bats. Using an evolutionary model that accounts for variation in the pressure of natural selection across sites and branches, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago, with a lower bound estimate of ∼5200 years before present.

abstract:
  Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity.


id: cord-319460-n4ezxnjc
title: Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study
author: Bertasio, Cristina
date: 2016-12-15
url: https://www.ncbi.nlm.nih.gov/pubmed/28018330/
doi: 10.3389/fmicb.2016.02009
abstract:
  The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.


id: cord-319614-4qi59pbz
author: Benej, Martin
date: 2019-10-25
txt: ./txt/cord-319614-4qi59pbz.txt
cache: ./cache/cord-319614-4qi59pbz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31708904/
doi: 10.3389/fmicb.2019.02438
summary:
  Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. These data suggest that LCMV maintains its replication in persistently infected cells by regulating redox signaling through modulation of local levels of H 2 O 2 and subsequent activation of cellular processes that it uses for its own benefit. Notably, the treatment with antioxidants also resulted in reduced levels of viral NP in HeLa, as well as in A549 LCMV-infected cells, suggesting a link between ROS-dependent signaling and virus replication (Figures 7B,D and Supplementary Figure S2B ).

title:
  Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells

abstract:
  Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. In order to shed more light on these processes, two-dimensional differential in-gel electrophoresis (2D-DIGE) and MALDI-TOF tandem mass spectrometry were used to determine the proteome response of the HeLa cell line to persistent LCMV infection. Quantitative analysis revealed 24 differentially abundant proteins. Functional analysis showed that LCMV-responsive proteins were primarily involved in metabolism, stress, and the defense response. Among identified proteins, we discovered significant changes for peroxiredoxins, a family of antioxidant enzymes. Decreased amount of these antioxidant proteins correlated with elevation of reactive oxygen species (ROS) in infected cells. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Moreover, treatment with antioxidants resulted in reduced levels of viral nucleoprotein, indicating a connection between ROS-dependent signaling and viral replication.


id: cord-321112-w7x1dkds
title: IFITM Genes, Variants, and Their Roles in the Control and Pathogenesis of Viral Infections
author: Zhao, Xuesen
date: 2019-01-08
url: https://doi.org/10.3389/fmicb.2018.03228
doi: 10.3389/fmicb.2018.03228
abstract:
  Interferon-induced transmembrane proteins (IFITMs) are a family of small proteins that localize in the plasma and endolysosomal membranes. IFITMs not only inhibit viral entry into host cells by interrupting the membrane fusion between viral envelope and cellular membranes, but also reduce the production of infectious virions or infectivity of progeny virions. Not surprisingly, some viruses can evade the restriction of IFITMs and even hijack the antiviral proteins to facilitate their infectious entry into host cells or promote the assembly of virions, presumably by modulating membrane fusion. Similar to many other host defense genes that evolve under the selective pressure of microorganism infection, IFITM genes evolved in an accelerated speed in vertebrates and many single-nucleotide polymorphisms (SNPs) have been identified in the human population, some of which have been associated with severity and prognosis of viral infection (e.g., influenza A virus). Here, we review the function and potential impact of genetic variation for IFITM restriction of viral infections. Continuing research efforts are required to decipher the molecular mechanism underlying the complicated interaction among IFITMs and viruses in an effort to determine their pathobiological roles in the context of viral infections in vivo.


id: cord-322649-c99lszcu
author: Miao, Faming
date: 2019-05-15
txt: ./txt/cord-322649-c99lszcu.txt
cache: ./cache/cord-322649-c99lszcu.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2019.01004
doi: 10.3389/fmicb.2019.01004
summary:
  title: Rapid and Sensitive Recombinase Polymerase Amplification Combined With Lateral Flow Strip for Detecting African Swine Fever Virus In this study, we developed a rapid test that combines recombinase polymerase amplification (RPA) of the ASFV p72 gene with lateral flow detection (LFD). Results showed that the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD) for ASFV was 150 copies per reaction within 10 min at 38°C. A dilution range of 10 0 to 10 5 copies per reaction of pMD19-p72 recombinant plasmid was used to evaluate the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD), and the amplicons were evaluated through agarose gel electrophoresis. The sensitivity results showed that the detection limit of the ASFV RPA-LFD assay was 10 2 copies per reaction of the recombinant plasmid pMD19-p72. Development of a TaqMan PCR assay with internal amplification control for the detection of African swine fever virus A recombinase polymerase amplification-based assay for rapid detection of African swine fever virus

title:
  Rapid and Sensitive Recombinase Polymerase Amplification Combined With Lateral Flow Strip for Detecting African Swine Fever Virus

abstract:
  African swine fever virus (ASFV), the etiological agent of African swine fever (ASF), a hemorrhagic fever of domestic pigs, has devastating consequences for the pig farming industry. More than 1,000,000 pigs have been slaughtered since 3 August 2018 in China. However, vaccines or drugs for ASF have yet to be developed. As such, a rapid test that can accurately detect ASFV on-site is important to the timely implementation of control measures. In this study, we developed a rapid test that combines recombinase polymerase amplification (RPA) of the ASFV p72 gene with lateral flow detection (LFD). Results showed that the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD) for ASFV was 150 copies per reaction within 10 min at 38°C. The assay was highly specific to ASFV and had no cross-reactions with other porcine viruses, including classical swine fever virus (CSFV). A total of 145 field samples were examined using our method, and the agreement of the positive rate between RPA-LFD (10/145) and real-time PCR (10/145) was 100%. Overall, RPA-LFD provides a novel alternative for the simple, sensitive, and specific identification of ASFV and showed potential for on-site ASFV detection.


id: cord-324058-20drr99p
title: Respiratory Microbial Co-infection With SARS-CoV-2
author: Massey, Bill W.
date: 2020-08-25
txt: ./txt/cord-324058-20drr99p.txt
cache: ./cache/cord-324058-20drr99p.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2020.02079
doi: 10.3389/fmicb.2020.02079
summary:
  We determined the prevalence and type of a wide variety of respiratory pathogens in 12,075 United States subjects tested for SARS-CoV-2 infection in March and April 2020. In the present study, we present data on the prevalence of SARS-CoV-2 and other bacterial, viral and fungal respiratory pathogens in samples taken from over 12,000 United States symptomatic subjects tested for the presence of SARS-CoV-2 in a manner which permitted assessment of the presence of co-pathogens as well as SARS-CoV-2. The t-test for independent group comparison was used to compare age of the study subjects across gender, SARS-CoV-2 ± patients and residential versus outpatients. The higher coinfection rate observed in the present study may be due to the criteria applied to SARS-CoV-2 testing eligibility at the time, which was heavily weighted toward symptomatic patients, and whom would be more likely to have a current infection. The infection rate for these other respiratory pathogens throughout the United States is much greater than that of SARS-CoV-2 itself in subjects seeking SARS-CoV-2 testing.

abstract:
  Co-infection with additional pathogens is a well-known feature of pandemics. We determined the prevalence and type of a wide variety of respiratory pathogens in 12,075 United States subjects tested for SARS-CoV-2 infection in March and April 2020. Infections with other respiratory pathogens, which on their own produce at least some SARS-CoV-2 symptoms including mortality, were present in both SARS-CoV-2 + and SARS-CoV-2- subjects. Non-SARS-CoV-2 infection rates were significantly higher in SARS-CoV-2 + (86%) patients than SARS-CoV-2– patients (76%) (p < 0.0001). Among the co-pathogens present in both subject groups were K. pneumoniae and M. catarrhalis which can produce serious respiratory illness on their own, Advanced age and nursing home status were associated with higher SARS-CoV-2 + and co-infection rates. Testing for the presence of co-pathogens going forward will assist in the diagnosis and optimal treatment of suspected SARS-CoV-2 respiratory infections in the current pandemic.


id: cord-324651-8teb5jrn
author: Filippini, Antonio
date: 2020-04-30
url: https://doi.org/10.3389/fmicb.2020.00970
doi: 10.3389/fmicb.2020.00970
abstract: nan
title:
  Could the Inhibition of Endo-Lysosomal Two-Pore Channels (TPCs) by the Natural Flavonoid Naringenin Represent an Option to Fight SARS-CoV-2 Infection?


id: cord-326217-ji0njeha
title: Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122
author: Saleh, Maged
date: 2018-11-27
txt: ./txt/cord-326217-ji0njeha.txt
cache: ./cache/cord-326217-ji0njeha.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30542341/
doi: 10.3389/fmicb.2018.02949
summary:
  We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. To assess whether both GSK3 isoforms are required for HCV replication, we silenced GSK3α and / or GSK3β gene expression by transfecting siRNAs and quantified HCV RNA in Huh-7.5 cells harboring HCV subgenomic replicon (Con1) or infectious HCV (Jc1). Given the well-known dependency of HCV on miR-122 (Jopling et al., 2005 (Jopling et al., , 2008 Machlin et al., 2011) and the regulatory circuit between insulin-like growth factor 1 receptor, GSK3β, and miR-122 identified previously (Zeng et al., 2010) , we assessed the effect of GSK3 inhibition on miR-122 expression in Huh-7.5 cells harboring a subgenomic HCV replicon.

abstract:
  Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.


id: cord-329003-ovnzlpa2
title: Rabbit Hemorrhagic Disease Virus Non-structural Protein 6 Induces Apoptosis in Rabbit Kidney Cells
author: Chen, Mengmeng
date: 2019-01-09
url: https://doi.org/10.3389/fmicb.2018.03308
doi: 10.3389/fmicb.2018.03308
abstract:
  Rabbit hemorrhagic disease (RHD) is a highly contagious disease caused by rabbit hemorrhagic disease virus (RHDV). Previous research has shown that RHDV induces apoptosis in numerous cell types, although the molecular mechanisms underlying the apoptosis induced by RHDV are not well understood. One possible factor is non-structural protein 6 (NSP6), a 3C-like protease that plays an important role in processing viral polyprotein precursors into mature non-structural proteins. To fully establish a role for NSP6, the present study examined the effects of ectopic expression of the protein in rabbit (RK13) and human (HeLa and HepG2) cells. We found that NSP6 suppressed cell viability and promoted apoptosis in all three cell types in a dose-dependent manner. We also identified increased caspase-3, -8, and -9 activities in RK13 cell, and an increased Bax to Bcl2 mRNA ratio. Mechanistically, the ability of NSP6 to induce apoptosis was impaired by mutation of the catalytic His27 residue. Our study has shown that RHDV NSP6 can induce apoptosis in host cells and is likely an important contributor to RHDV-induced apoptosis and pathogenesis.


id: cord-330942-x238hq9b
author: Versluys, Anne Birgitta
date: 2018-11-21
url: https://doi.org/10.3389/fmicb.2018.02795
doi: 10.3389/fmicb.2018.02795
title:
  Morbidity and Mortality Associated With Respiratory Virus Infections in Allogeneic Hematopoietic Cell Transplant: Too Little Defense or Harmful Immunity?

abstract:
  The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Here we give an overview of the current literature on the incidence and chance of progression to severe disease in this highly immune compromised population. We discuss the issue whether it is predominantly direct viral damage that causes clinical deterioration, or that it is in fact the allogeneic immuneresponse to the virus that is most important. This is an important question as it will guide therapeutic decision making. It asks for further collaborative studies focusing on sensitive surveillance with PCR techniques and relating clinical data with parameters of immune reconstitution.


id: cord-331973-avjw4kx1
title: Laboratory Diagnosis of Respiratory Tract Infections in Children – the State of the Art
author: Das, Shubhagata
date: 2018-10-18
txt: ./txt/cord-331973-avjw4kx1.txt
cache: ./cache/cord-331973-avjw4kx1.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2018.02478
doi: 10.3389/fmicb.2018.02478
summary:
  Serological tests can successfully identify antibodies to most respiratory pathogens such as RSV, adenovirus, influenza A and B, parainfluenza 1-3 virus, etc., and can detect mixed infections from hospitalized children suffering from acute respiratory infections, with the exception of infants for whom an antibody response is usually undetected (Hall et al., 1991; Chkhaidze et al., 2006) . FA testing, in addition to RT-PCR, is useful for epidemiological studies as it increases the probability of identifying acute viral infections and has been used for accurate assessment of respiratory viruses other than influenza in children (Sawatwong et al., 2012; Feikin et al., 2013; Zhang et al., 2017) . Most of the studies evaluating the clinical performance of these assays have reported high sensitivity (87-100%) and specificity (>98%) for detecting influenza A/B and RSV in pediatric and adult patients (Bell et al., 2014; Nie et al., 2014; Popowitch and Miller, 2015; Gibson et al., 2017; Ling et al., 2018) .

abstract:
  In the pediatric population, respiratory infections are the most common cause of physician visits. Although many respiratory illnesses are self-limiting viral infections that resolve with time and supportive care, it can be critical to identify the causative pathogen at an early stage of the disease in order to implement effective antimicrobial therapy and infection control. Over the last few years, diagnostics for respiratory infections have evolved substantially, with the development of novel assays and the availability of updated tests for newer strains of pathogens. Newer laboratory methods are rapid, highly sensitive and specific, and are gradually replacing the conventional gold standards, although the clinical utility of these assays is still under evaluation. This article reviews the current laboratory methods available for testing for respiratory pathogens and discusses the advantages and disadvantages of each approach.


id: cord-332221-6ea6gz9s
author: Li, Guiping
date: 2019-11-26
txt: ./txt/cord-332221-6ea6gz9s.txt
cache: ./cache/cord-332221-6ea6gz9s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31849847/
doi: 10.3389/fmicb.2019.02541
summary:
  The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. To explore the mechanism by which IGF1 regulates acute inflammatory lung injury induced by IAV infection, a Western blot was used to detect the expression of molecules in key signaling pathways in the lung tissue of PR8-infected mice (50LD 50 PR8).

title:
  Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection

abstract:
  The acute inflammatory lung injury is an important cause of death due to influenza A virus (IAV) infection. Insulin-like growth factor 1 (IGF1) played an important role in the regulation of inflammation in the immune system. To investigate the role of IGF1 in IAV-mediated acute inflammatory lung injury, the expression of IGF1 and inflammatory cytokines was tested after IAV A/Puerto Rico/8/1934 (H1N1; abbreviated as PR8) infection in A549 cells. Then, a BALB/c mouse model of PR8 infection was established. On days 3, 5, 7, and 9 post-infection, the mice lung tissue was collected to detect the expression changes in IGF1 mRNA and protein. The mice were divided into four groups: (1) PBS (abbreviation of phosphate buffered saline); (2) PR8 + PBS; (3) PR8 + IGF1; and (4) PR8 + PPP (abbreviation of picropodophyllin, the IGF1 receptor inhibitor). The body weight and survival rate of the mice were monitored daily, and the clinical symptoms of the mice were recorded. On day 5 post-infection, the mice were sacrificed to obtain the serum and lung tissues. The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. It was found that IGF1 expression is upregulated in A549 cells and BALB/c mice infected with PR8, whereas IGF1 regulated the expression of inflammatory cytokines induced by PR8 infection. Overexpression of IGF1 aggravated the IAV-mediated inflammatory response, whereas the inhibition of IGF1 receptor reduced such inflammatory response. The phosphorylation of IGF1 receptor triggered the PI3K/AKT and MAPK signaling pathways to induce an inflammatory response after IAV infection. Therefore, IGF1 plays an important immune function in IAV-mediated acute inflammatory lung injury. IGF1 may provide a therapeutic target for humans in response to an influenza outbreak, and inhibition of IGF1 or IGF1 receptor may represent a novel approach to influenza treatment.


id: cord-333309-21czobqy
title: ERAD and how viruses exploit it
author: Byun, Hyewon
date: 2014-07-03
txt: ./txt/cord-333309-21czobqy.txt
cache: ./cache/cord-333309-21czobqy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25071743/
doi: 10.3389/fmicb.2014.00330
summary:
  Interaction of lectin-type and other chaperones with ERAD substrates allows association with members of the protein disulfide isomerase (PDI) family, which generally are characterized by one or more thioredoxin-like motifs (CXXC; Brodsky and Skach, 2011) . In contrast to the rhomboid proteases, the Derlins lack proteolytic activity, suggesting that these proteins bind to ERAD substrates and target them to E3 ligases for ubiquitination and to p97 for membrane extraction (Brodsky, 2012) . These ubiquitin ligases are members of the cytosolic SCF (S-phase kinase-associated protein 1 (Skp1)-Cullin 1 (Cul1)-F-box) family, where the F-box components of the SCF complex recognize the N-glycans of the retrotranslocated substrate, e.g., Fbs1 and Fbs2 (Yoshida, 2007) . A proteasomal ATPase contributes to dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins

abstract:
  Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response.


id: cord-336074-76ca1cfy
author: Izumida, Mai
date: 2016-01-19
url: https://www.ncbi.nlm.nih.gov/pubmed/26834711/
doi: 10.3389/fmicb.2015.01552
title:
  Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis

abstract:
  Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within.


id: cord-337198-4sors3bg
author: Clementi, Nicola
date: 2020-07-10
txt: ./txt/cord-337198-4sors3bg.txt
cache: ./cache/cord-337198-4sors3bg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32754147/
doi: 10.3389/fmicb.2020.01704
summary:
  In this study, we evidence that the anti-SARS-CoV2 activity of a clinically achievable hydroxychloroquine concentration is maximized only when administered before and after the infection of Vero E6 and Caco-2 cells. In this study, we tested HCQ against a SARS-CoV-2 Italian clinical isolate, by using different protocols of drug administration corresponding to its possible prophylactic, therapeutic, and prophylactic/therapeutic use in patients. A clinical isolate hCoV-19/Italy/UniSR1/2020 (GISAID accession ID: EPI_ISL_413489) was isolated and propagated in Vero E6 cells, and viral titer was determined by 50% tissue culture infective dose (TCID 50 ) and plaque assay for confirming the obtained titer. HCQ EC 50 against SARS-CoV-2 was obtained by both CPE and RT-PCR analysis on results from full-time experimental setting on Vero E6 cells. Different concentrations of HCQ were tested on Vero E6 to determine the effective concentration of the drug against SARS-CoV-2 in vitro infection (Figure 1) .

title:
  Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro

abstract:
  While the SARS-CoV-2 pandemic is heavily hitting the world, it is of extreme importance that significant in vitro observations guide the quick set up of clinical trials. In this study, we evidence that the anti-SARS-CoV2 activity of a clinically achievable hydroxychloroquine concentration is maximized only when administered before and after the infection of Vero E6 and Caco-2 cells. This suggests that only a combined prophylactic and therapeutic use of hydroxychloroquine may be effective in limiting viral replication in patients.


id: cord-338773-ilir895i
author: Wu, Zhiqiang
date: 2018-10-24
txt: ./txt/cord-338773-ilir895i.txt
cache: ./cache/cord-338773-ilir895i.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30405596/
doi: 10.3389/fmicb.2018.02562
summary:
  Novel sequencing reads related to pestivirus were found in samples collected from different bat and rodent species. Genomic and phylogenetic analyses of these viruses revealed the presences of six novel pestivirus species in bat and rodent hosts. Each peptide of BPV species 1 and 2 aligned best with those of APPV, even when the overall identities FIGURE 1 | Occurrence of pestivirus-related reads in bats and rodents from different locations. This study described the identification of novel BPVs and RPVs in different bat and rodent species across several Chinese regions, which revealed that these two mammals served as natural hosts for pestiviruses. Considering their divergent phylogenetic positions, different genome sizes and structures, and the minimal sequence similarities of BPVs and RPVs when compared to other pestiviruses, we propose classifying members of the genus Pestivirus into three main lineages; bat-swine, rodent, and artiodactylous lineages, based on the order level of their hosts.

title:
  Discovery of Diverse Rodent and Bat Pestiviruses With Distinct Genomic and Phylogenetic Characteristics in Several Chinese Provinces

abstract:
  Bats and rodents are widely distributed worldwide and can be native or intermediate reservoirs of many important zoonotic viruses. Pestiviruses are a group of virus species of the genus Pestivirus under the family Flaviviridae that can infect a wide variety of artiodactylous hosts, including swine and ruminants. Two classic types of pestiviruses, bovine viral diarrhea virus and classical swine fever virus, are important causative agents of mild-to-severe disease in bovine and swine hosts, respectively, and cause tremendous economic losses in these industries. Recent reports revealed that bats and rodents could also act as natural hosts of pestiviruses and an atypical porcine pestivirus, which cause disease in piglets, showed a close genetic relationship with a specific bat pestivirus, RaPestV-1. This study aimed to describe the detection and characterization of novel pestiviruses from bats and rodents in different locations by analyzing the available bat and rodent virome data from throughout China. Two bat pestivirus species and four rodent pestivirus species that are distinct from other known viruses were identified and sequenced. These viruses were identified from two bat species and four rodent species in different Chinese provinces. There were two distinct lineages present in these viruses, that differ from artiodactylous pestivirus. These findings expand our understanding of the genetic diversity of pestiviruses in bats and rodents and suggest the presence of a diverse set of pestiviruses in non-artiodactylous hosts. This study may provide new insight for the prevention of future viral disease outbreaks originating from bats and rodents.


id: cord-343132-qqhivgkq
author: Chang-Liao, Wan-Ping
date: 2020-07-15
txt: ./txt/cord-343132-qqhivgkq.txt
cache: ./cache/cord-343132-qqhivgkq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32760370/
doi: 10.3389/fmicb.2020.01578
summary:
  The results showed that the intracellular extracts of Ln. mesenteroides YPK30 possessed in vitro prophylactic, therapeutic, and direct-inhibitory effects against PEDV in the Vero cell model. As shown in Figure 3 , the metabolic activity of Vero cells pretreated with the intracellular extracts of Ln. mesenteroides, regardless of which strain, were similar to those pretreated with IFN-α2b (p > 0.05) but were significantly higher than the un-pretreated cells (p < 0.05), indicating that all the Ln. mesenteroides strains isolated from kefir grains possessed in vitro prophylactic effects against PEDV. durans, Lb. kefiri, Lc. lactis, and Ln. mesenteroides , were isolated from kefir grains, and the in vitro prophylactic effects of the intracellular extracts of these four species against PEDV infection in Vero cells were compared. Therefore, the in vitro prophylactic and therapeutic effects of the intracellular extracts of Ln. mesenteroides YPK30 against PEDV in Vero cells seem not be attributed to the direct interaction of bacterial components or metabolites with virus.

title:
  Isolation of a Leuconostoc mesenteroides Strain With Anti-Porcine Epidemic Diarrhea Virus Activities From Kefir Grains

abstract:
  Swine grown under commercial conditions are vulnerable to environmental exposure to several viruses, which may cause infectious diseases and spread easily and rapidly, resulting in significant economic losses in animal husbandry. Previous studies have suggested that probiotics seem to be a new and promising alternative to vaccinations to protect animals against potential viral infections. In this study, we used the Vero cell culture model of infection to study porcine epidemic diarrhea virus (PEDV). We screened lactic acid bacteria (LAB) with anti-PEDV potential from kefir grains, which are starter cultures used to ferment milk into kefir. Twenty-nine LAB strains were isolated and identified as Enterococcus durans, Lactobacillus kefiri, Lactococcus lactis, and Leuconostoc mesenteroides, according to 16S ribosomal RNA (rRNA) and rpoA gene sequence analyses. The anti-PEDV activities of the LAB intracellular extracts were compared, and the intracellular extracts of Ln. mesenteroides showed higher anti-PEDV activities than that of the other species. Among the Ln. mesenteroides strains, a strain designated YPK30 showed a higher growth rate than that of the other strains and was further evaluated for its anti-PEDV activity. The results showed that the intracellular extracts of Ln. mesenteroides YPK30 possessed in vitro prophylactic, therapeutic, and direct-inhibitory effects against PEDV in the Vero cell model. The expression levels of Type 1 interferon (IFN)-dependent genes, including Myxovirus resistance 1 (MX1) and interferon-stimulated gene 15 (ISG15), were significantly increased after treatment with intracellular extracts of Ln. mesenteroides YPK30 for 24 h. Such expression suggests that the anti-PEDV activity of Ln. mesenteroides YPK30 could be attributed to its up-regulatory effect on the expression of MX1 and ISG15 genes. These results suggested that Ln. mesenteroides YPK30 has the potential to provide some levels of host protection against PEDV infections.


id: cord-343357-5nhyumxl
author: Heegaard, Peter M. H.
date: 2020-09-25
txt: ./txt/cord-343357-5nhyumxl.txt
cache: ./cache/cord-343357-5nhyumxl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2020.573756
doi: 10.3389/fmicb.2020.573756
summary:
  We urge considering infection with porcine respiratory coronavirus of metabolic syndrome pigs, such as the obese Ossabaw pig, as a highly relevant animal model of severe COVID-19. Cytokine storm in the lungs and inflammation are suggested as essential for the escalating and prolonged lung disease observed in severely affected COVID-19 patients, as is also the case for other severe human coronavirus infections like SARS and MERS (Mehta et al., 2020) . We hypothesize that disease severity will increase in obese Ossabaw pigs infected with PRCV compared to pigs of normal weight, and hence will constitute a useful model for severe COVID-19 in humans at risk due to metabolic syndrome associated comorbidities, including aged individuals. With the added benefit of being a well-described pig-specific virus (with no rigorous biosafety demands), we suggest that the obese pig affected by the metabolic syndrome will constitute a highly human-translatable animal model having the potential to significantly facilitate and accelerate SARS-CoV-2/COVID-19 research.

title:
  Animal Models for COVID-19: More to the Picture Than ACE2, Rodents, Ferrets, and Non-human Primates. A Case for Porcine Respiratory Coronavirus and the Obese Ossabaw Pig

abstract:
  The ongoing COVID-19 pandemic caused by infection with SARS-CoV-2 has created an urgent need for animal models to enable study of basic infection and disease mechanisms and for development of vaccines, therapeutics, and diagnostics. Most research on animal models for COVID-19 has been directed toward rodents, transgenic rodents, and non-human primates. The primary focus has been on the angiotensin-converting enzyme 2 (ACE2), which is a host cell receptor for SARS-CoV-2. Among investigated species, irrespective of ACE2 spike protein binding, only mild (or no) disease has occurred following infection with SARS-CoV-2, suggesting that ACE2 may be necessary for infection but is not sufficient to determine the outcome of infection. The common trait of all species investigated as COVID models is their healthy status prior to virus challenge. In contrast, the vast majority of severe COVID-19 cases occur in people with chronic comorbidities such as diabetes, obesity, and/or cardiovascular disease. Healthy pigs express ACE2 protein that binds the viral spike protein but they are not susceptible to infection with SARS-CoV-2. However, certain pig breeds, such as the Ossabaw pig, can reproducibly be made obese and show most aspects of the metabolic syndrome, thus resembling the more than 80% of the critically ill COVID-19 patients admitted to hospitals. We urge considering infection with porcine respiratory coronavirus of metabolic syndrome pigs, such as the obese Ossabaw pig, as a highly relevant animal model of severe COVID-19.


id: cord-344200-ev4707pq
author: Yu, Qing
date: 2020-06-19
txt: ./txt/cord-344200-ev4707pq.txt
cache: ./cache/cord-344200-ev4707pq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2020.01206
doi: 10.3389/fmicb.2020.01206
summary:
  title: Specific Aptamer-Based Probe for Analyzing Biomarker MCP Entry Into Singapore Grouper Iridovirus-Infected Host Cells via Clathrin-Mediated Endocytosis Aptamer-Q5-complexed major capsid protein (MCP) in the membrane of SGIV-infected cells can be used as a specific molecular probe to investigate the crucial events of MCP endocytosis into SGIV-infected host cells during viral infection. Therefore, MCP enters SGIV-infected host cells via clathrin-mediated endocytosis, which is dependent on dynamin, cholesterol, low pH, and cytoskeletal actin filaments. In this study, an aptamer (Q5)-based specific probe was used to investigate the trafficking mechanism and endocytotic pathway of MCP in host cells during SGIV infection. We analyzed the effects of various inhibitors on the binding of aptamer Cy5-Q5 to its target protein, MCP, in the membranes of SGIV-infected cells with flow cytometry. Relative to the control group of normal GS cells, the GS cells incubated with the safe working concentration of each inhibitor in L-15 medium retained their normal FIGURE 7 | Caveolae/raft-dependent endocytosis is not involved in MCP entry during SGIV infection.

title:
  Specific Aptamer-Based Probe for Analyzing Biomarker MCP Entry Into Singapore Grouper Iridovirus-Infected Host Cells via Clathrin-Mediated Endocytosis

abstract:
  Biomarkers have important roles in various physiological functions and disease pathogenesis. As a nucleocytoplasmic DNA virus, Singapore grouper iridovirus (SGIV) causes high economic losses in the mariculture industry. Aptamer-Q5-complexed major capsid protein (MCP) in the membrane of SGIV-infected cells can be used as a specific molecular probe to investigate the crucial events of MCP endocytosis into SGIV-infected host cells during viral infection. Chlorpromazine blocks clathrin-mediated endocytosis, and MCP endocytosis into SGIV-infected cells decreased significantly when the cells were pretreated with chlorpromazine. The disruption of cellular cholesterol by methyl-β-cyclodextrin also significantly reduced MCP endocytosis. In contrast, inhibitors of key regulators of caveolae/raft-dependent endocytosis and macropinocytosis, including genistein, Na(+)/H(+) exchanger, p21-activated kinase 1 (PAK1), myosin II, Rac1 GTPase, and protein kinase C (PKC), had no effect on MCP endocytosis. The endocytosis of the biomarker MCP is dependent on low pH and cytoskeletal actin filaments, as shown with various inhibitors (chloroquine, ammonia chloride, cytochalasin D). Therefore, MCP enters SGIV-infected host cells via clathrin-mediated endocytosis, which is dependent on dynamin, cholesterol, low pH, and cytoskeletal actin filaments. This is the first report of a specific aptamer-based probe used to analyze MCP endocytosis into SGIV-infected host cells during viral infection. This method provides a convenient strategy for exploring viral pathogenesis and facilitates the development of diagnostic tools for and therapeutic approaches to viral infection.


id: cord-344970-ud1lhkyi
title: Coronavirus Interplay With Lipid Rafts and Autophagy Unveils Promising Therapeutic Targets
author: Fecchi, Katia
date: 2020-08-11
txt: ./txt/cord-344970-ud1lhkyi.txt
cache: ./cache/cord-344970-ud1lhkyi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32849425/
doi: 10.3389/fmicb.2020.01821
summary:
  Lipid rafts are specialized plasma membrane microdomains involved in important processes of the virus infections and of the host target cells (Rosenberger et al., 2000) . This minireview reports on the available knowledge about the interplay between coronaviruses, including the SARS-CoV-2, with lipid rafts and autophagic pathways, in order to focus the attention to novel potential targets to inhibit coronavirus infections. As outlined in this review, lipid rafts and autophagic pathways play a pivotal role in coronavirus infection, being critical for viral entry and replication, as well as for viral release from the host cells. In fact, different drugs described as inhibitors or inducers of the autophagy that control host cell pathways process involved in coronavirus infection, have sparked interest for their potential antiviral activity (Shakya et al., 2018; Liu et al., 2019; Xu et al., 2020; Yang et al., 2020 ; Table 1 ).

abstract:
  Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses that can infect animal and human hosts. The infection induces mild or sometimes severe acute respiratory diseases. Nowadays, the appearance of a new, highly pathogenic and lethal coronavirus variant, SARS-CoV-2, responsible for a pandemic (COVID-19), represents a global problem for human health. Unfortunately, only limited approaches are available to treat coronavirus infections and a vaccine against this new coronavirus variant is not yet available. The plasma membrane microdomain lipid rafts have been found by researchers to be involved in the replication cycle of numerous viruses, including coronaviruses. Indeed, some pathogen recognition receptors for coronaviruses as for other viruses cluster into lipid rafts, and it is therefore conceivable that the first contact between virus and host cells occurs into these specialized regions, representing a port of cell entry for viruses. Recent data highlighted the peculiar pro-viral or anti-viral role played by autophagy in the host immune responses to viral infections. Coronaviruses, like other viruses, were reported to be able to exploit the autophagic machinery to increase their replication or to inhibit the degradation of viral products. Agents known to disrupt lipid rafts, such as metil-β-cyclodextrins or statins, as well as autophagy inhibitor agents, were shown to have an anti-viral role. In this review, we briefly describe the involvement of lipid rafts and autophagy in coronavirus infection and replication. We also hint how lipid rafts and autophagy may represent a potential therapeutic target to be investigated for the treatment of coronavirus infections.


id: cord-347917-fmb5nyxu
author: Liu, Junli
date: 2020-01-28
txt: ./txt/cord-347917-fmb5nyxu.txt
cache: ./cache/cord-347917-fmb5nyxu.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2019.03036
doi: 10.3389/fmicb.2019.03036
summary:
  In this study, genome-wide profiling of lncRNAs in swine testicular (ST) cells infected with PDCoV was performed using RNA-seq. An integrative analysis of lncRNA alterations suggested their putative role in regulating the expression of several key genes in metabolic and TNF signaling pathways during infection. There have been reports of using genome-wide association analysis between lncRNAs and the co-expressed and/or co-regulated protein-coding genes to characterize the function of the lncRNA (Huarte et al., 2010) . GO and KEGG pathway enrichment analysis of target genes revealed that lncRNAs may act in cis or trans to participate in the regulation of expression of multiple important genes in different processes including protein binding, DNA transcription, metabolism, and immune response. The functional association between regulatory lncRNA and protein-coding gene transcripts can be determined by performing expression correlation analysis coupled with ascertaining their putative role in related physiological processes.

title:
  Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection

abstract:
  Porcine delta coronavirus (PDCoV) is a novel emerging enterocytetropic virus causing diarrhea, vomiting, dehydration, and mortality in suckling piglets. Long non-coding RNAs (lncRNAs) are known to be important regulators during virus infection. Here, we describe a comprehensive transcriptome profile of lncRNA in PDCoV-infected swine testicular (ST) cells. In total, 1,308 annotated and 1,190 novel lncRNA candidate sequences were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these lncRNAs might be involved in numerous biological processes. Clustering analysis of differentially expressed lncRNAs showed that 454 annotated and 376 novel lncRNAs were regulated after PDCoV infection. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to metabolism and TNF signaling. Our study provided comprehensive information about lncRNAs that would be a useful resource for studying the pathogenesis of and designing antiviral therapy for PDCoV infection.


id: cord-351719-xqmir1ca
title: Food Safety During and After the Era of COVID-19 Pandemic
author: Olaimat, Amin N.
date: 2020-08-04
url: https://www.ncbi.nlm.nih.gov/pubmed/32849446/
doi: 10.3389/fmicb.2020.01854
abstract:
  The coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 due to its rapid and extensive spread among many countries through its very contagious nature and its high mortality among the elderly and infirm. Recently, data on the survival of SARS-CoV-2 on contact surfaces has been reported, but there is none on the survival of COVID-19 on food surfaces and packages. The potential survival and transmission of SARS-CoV-2 on/via food and packages are discussed based on data available for other respiratory viruses such as SARS-CoV and MERS-CoV. However, studies are needed to explore its transmission via food and survival on food packaging materials. The implementation of food safety management systems such as Hazard Analysis and Critical Control Points (HACCP), and Good Manufacturing Practices (GMP) are important to reduce the risk of COVID-19 infection. Cleaning, sanitation, good hygienic practices, and active packaging are also needed from farm to fork.


id: cord-353454-zq51hpjs
title: Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance
author: Gouda, Sushanto
date: 2016-09-29
txt: ./txt/cord-353454-zq51hpjs.txt
cache: ./cache/cord-353454-zq51hpjs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27746767/
doi: 10.3389/fmicb.2016.01538
summary:
  While plant sources are being extensively explored for the discovery of new chemical entities for various therapeutic purposes, endophytic microorganisms play an important role in this search for natural bioactive compounds, with potential use in the health sector and in drug discovery (Lam, 2007) . Bacterial endophytes are diverse in nature and are known to produce different bioactive metabolites that act as antimicrobial and anticancer compounds, for example, with 76% of them reported from the single genus, Streptomyces (Berdy, 2012) . Endophytes are reported to produce a number of bioactive metabolites in a single plant or microbe which served as an excellent source of drugs for treatment against various diseases and with potential applications in agriculture, medicine, food and cosmetics industries (Strobel and Daisy, 2003; Jalgaonwala et al., 2011; Godstime et al., 2014; Shukla et al., 2014) .

abstract:
  Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use.


id: cord-353815-w35spqqt
author: Huan, Yuchen
date: 2020-10-16
txt: ./txt/cord-353815-w35spqqt.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33178164/
doi: 10.3389/fmicb.2020.582779
summary:
  This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. Tryptophan (Trp), as a non-polar amino acid, has a remarkable effect on the interface region of the lipid bilayer, whereas Arg, as a basic amino acid, confers peptide charge and hydrogen bond interactions, which are essential properties to combine with the bacterial membrane''s abundant anionic component. And it seems that Trp residues play the role of natural aromatic activators of Arg-rich AMPs by ion-pair-π interactions (Walrant et al., 2020) , thereby promoting enhanced peptide-membrane interactions (Chan et al., 2006) . Furthermore, L4H4, which is designed based on the linear cationic amphiphilic peptide magainin, also shows good antibacterial activity and cell penetration properties by inserting four histidine sequences in leucine and alanine (Lointier et al., 2020) .

title:
  Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

abstract:
  Antimicrobial peptides (AMPs) are a class of small peptides that widely exist in nature and they are an important part of the innate immune system of different organisms. AMPs have a wide range of inhibitory effects against bacteria, fungi, parasites and viruses. The emergence of antibiotic-resistant microorganisms and the increasing of concerns about the use of antibiotics resulted in the development of AMPs, which have a good application prospect in medicine, food, animal husbandry, agriculture and aquaculture. This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. The research progress on antivirus peptides, especially anti-coronavirus (COVID-19) peptides, has been introduced given the COVID-19 pandemic worldwide in 2020.


id: cord-353957-0pjg25kn
author: Chen, Shilong
date: 2017-04-20
txt: ./txt/cord-353957-0pjg25kn.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28473814/
doi: 10.3389/fmicb.2017.00672
summary:
  Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection. Interestingly, we observed that ATMUV infection could trigger duck innate immune response including robust expression of particular type I and type III IFNs and IFITM family proteins. Our previous studies had shown that ATMUV infection effectively triggers the host innate immune response, including robust upregulation of type I and type III IFNs and some critical ISGs in chicken and CEF (Chen et al., 2016a) . To confirm these findings, DF-1 cell lines expressing specific shRNA targeting each of these IFITMs were infected with ATMUV and harvested at 36 hpi, followed by qRT-PCR assay to detect mRNA expression of viral genes.

title:
  Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection

abstract:
  Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues. Furthermore, we observed that expression of interferon-inducible transmembrane proteins (IFITMs) was significantly upregulated in DEF and DF-1 cells after infection with ATMUV. Similar results were obtained from in vivo studies using ATMUV-infected ducklings. Importantly, we showed that knockdown of endogenous IFITM1 or IFITM3 by specific shRNA markedly enhanced ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection.


