# ent

id: cord-259044-mubjm22l
type: CHEMICAL
entity:
  phenolic acid constituents like caffeic acid chlorogenic acid coumaric acid ferulic acid gallic acid


id: cord-259044-mubjm22l
type: CHEMICAL
entity:
  CA caffeic acid CH chlorogenic acid CO coumaric acid FE ferulic acid GA gallic acid p value 0 01 p value 0 001


id: cord-259044-mubjm22l
type: DISEASE
entity:
  influenza A H1N1 H3N2 virus and its inhibition of neuraminidase Antiviral activity of the Virus Blocking Factor VBF


id: cord-262760-mf1pn587
type: DNA
entity:
  NCBI Databank SARS CoV 2 Severe Acute Respiratory J o u r n a l P r e p r o o f Syndrome Coronavirus 2 Sequences


id: cord-262760-mf1pn587
type: PROTEIN
entity:
  coronavirus nucleocapsid protein COVID 19 pandemic Geneva World Health Organization Evidence for host dependent RNA editing


id: cord-268337-o6lo55o8
type: DISEASE
entity:
  HIV 2 human Tcell leukemia virus HTLV 1 simian immunodeficiency virus SIV Moloney murine leukemia virus


id: cord-252048-ftbjsoup
type: DNA
entity:
  IBV 5 RACE SP1 5 CGTATAGAAAAACAAAGCGTCAC 3 IBV 5 RACE SP2 5 GTCACTGTCTATTGTATGTCTGCTC 3 and IBV 5 RACE SP3 5 TAGCCGACCTTATGCGAGAACG 3


id: cord-252048-ftbjsoup
type: DNA
entity:
  Cal99 NE15172 95 IBV CK CA99 99 CA CA557 03 IBV Conn 66 IBV Conn 72 IBV Conn 83 IBV Conn 91 IBV Mass 65 IBV Mass 72 IBV Mass 79 IBV Mass 85 IBV Mass 06 and the IBV CK A2 China


id: cord-252048-ftbjsoup
type: DNA
entity:
  S1 gene b CAL 1 0 10 2 9 4 10 4 2 0 10 2 2 4 10 3 Conn 1 5 10 4 1 7 10 4 2 6 10 4 3 5 10 4 Mass 1 9 10 3 2 4 10 4 3 3 10 3 5 8 10 4


id: cord-252048-ftbjsoup
type: DNA
entity:
  envelope and membrane genes Coronavirus avian infectious bronchitis virus Infectious bronchitis virus evidence for recombination


id: cord-252048-ftbjsoup
type: WORK_OF_ART
entity:
  A Laboratory Manual for the Isolation Identification and Characterization of Avian Pathogens Recombinant


id: cord-268930-y1cm58r6
type: PROTEIN
entity:
  Cys proteinase CP nsp2 Cys proteinase SP nsp4 Ser proteinase RdRp RNA dependent RNA polymerase Z zinc finger Hel helicase N nidovirus specific endoribonuclease NendoU B


id: cord-259671-7de21oaq
type: PROTEIN
entity:
  viral N protein heterogeneous ribonucleoprotein hnRNP family members polypyrimidine tract binding protein


id: cord-259671-7de21oaq
type: PROTEIN
entity:
  protease ADP ribose 1 phosphatase NTPase 5 to 3 helicase RNA 5 triphosphatase RNA polymerase guanosine N7


id: cord-259671-7de21oaq
type: RNA
entity:
  SARS coronavirus RNA cap 2 O methyltransferase nsp10 nsp16 complex Coronavirus nonstructural protein 16


id: cord-259671-7de21oaq
type: CHEMICAL
entity:
  Octanucleotide A B C Fig 5 Alignment based secondary structure prediction of betacoronavirus 3 genome regions The viruses


id: cord-259671-7de21oaq
type: DISEASE
entity:
  coronavirus transcription A contemporary view of coronavirus transcription Selective replication of coronavirus genomes


id: cord-284479-75zgljet
type: CHEMICAL
entity:
  5 5 fluoro 2 oxo 1 2 dihydroindol 3Z ylidenemethyl 2 4 dimethyl 1H pyrrole 3 carboxylic acid 2 diethylaminoethyl amide


id: cord-267228-g2tf1jz6
type: DNA
entity:
  digested 2240 bp S gene fragment Spike Protein Gene GenBank JQ257007 1 source 75 2313 Spike Protein GenBank AEW24858 1 source 26 771 and DCpep S DCpep


id: cord-267228-g2tf1jz6
type: GGP
entity:
  pgsA P 0 05 or saline P 0 01 groups Fig 2C However no obvious differences were observed in CD11c CD86


id: cord-267228-g2tf1jz6
type: GGP
entity:
  pgsA P 0 05 and saline P 0 01 groups at day 35 Fig 4 In contrast no obvious difference was observed with respect to SlgA


id: cord-271568-qgpi2kcs
type: ORG
entity:
  A Laboratory Manual for the Isolation Identification and Characterization of Avian Pathogens Coronaviruses


id: cord-286658-9kco7qad
type: PROTEIN
entity:
  S2 4 8 12 16 20 24 28 4 8 12 16 20 24 28 32 36 40 44 I1101 16 10 10 3 10 10 b 9 10 7 10 6 10 2 10 1 10 1 10 7 10 8 10 10 10 7 10 7 10 5 10 6 10 6 10 6 10 2 10 0 10 ck CH LJL 140901 9 10 0 9 10 10 10 10 6 10 2 10 2 10 0 10 c 10 10 10 10 10 10 10 10 6 10 6 10 6 10 0 10 Negative 0 10 0 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10 0 10


id: cord-287324-ecpicv5v
type: ORG
entity:
  Baculoviridae Herpesviridae Iridoviridae Marseilleviridae Nodaviridae Papillomaviridae Partitiviridae Poxviridae and Totiviridae


id: cord-287324-ecpicv5v
type: ORG
entity:
  Paramyxoviridae Orthomyxoviridae Astroviridae Coronaviridae Potyviridae Tombusviridae Picobirnaviridae Reoviridae Adenoviridae


id: cord-290481-i2ppvsh5
type: CHEMICAL
entity:
  citrus tristeza virus RNA genome Transcriptional strategy of closteroviruses mapping the 5 termini of the citrus tristeza virus subgenomic RNAs The origin and early evolution of plants on land Genome structure


id: cord-290481-i2ppvsh5
type: CHEMICAL
entity:
  beet yellows virus the closterovirus type member Processing and subcellular localization of the leader papain like proteinase of Beet yellows closterovirus Sequence motifs involved in the regulation of discontinuous coronavirus subgenomic RNA synthesis The authors are grateful to Eugene V Koonin


id: cord-260422-z22t57ju
type: DISEASE
entity:
  human immunodeficiency virus type 1 genomic RNA The nucleocapsid protein specifically anneals tRNALys 3 onto a noncomplementary primer binding site within the HIV 1 RNA genome


id: cord-260422-z22t57ju
type: DISEASE
entity:
  Human immunodeficiency virus type 1 central DNA flap dynamic terminal product of plus strand displacement DNA synthesis


id: cord-279827-921kvrrz
type: DISEASE
entity:
  herpes simplex virus type 1 and pseudorabies virus The three major immediate early transcripts of bovine herpesvirus 1


id: cord-286473-sl5zy8nj
type: PROTEIN
entity:
  protein membrane M protein ORF5 ORFs X 5a 5b nucleocapsid N protein 3 UTR poly A TCoV genome structure


id: cord-286473-sl5zy8nj
type: DNA
entity:
  TCoV genome S spike glycoprotein gene 3a 3b and 3c E tricistronic gene 3 M membrane protein gene ORF X unique ORF


id: cord-286473-sl5zy8nj
type: PROTEIN
entity:
  FeCoV 46 43 59 40 37 43 38 HCoV 229E 60 45 59 40 40 43 40 HCoV NL63 50 45 60 41 42 44 39 BCoV NC 46 46 59 45 41 50 44 HCoV OC43 48 46 59 44 42 51 44 MHV JHM 46 43 58 43 43 51 42 SARS CoV 45 41 59 44 31 45 41 IBV Beaudette 94 90 93 57 90 94 92 IBV p65 87 90 93 57 88 92 92 IBV M41 87 90 93 57 88 92 93 TCoV MG10 100 100 100 100 100 100 100 TCoV G1


id: cord-286473-sl5zy8nj
type: DNA
entity:
  murine hepatitis virus MHV BCoV HCoV OC43 rat sialodacryoadenyleitis virus SADV canine respiratory coronavirus CRCoV


id: cord-286473-sl5zy8nj
type: PROTEIN
entity:
  ORF1b spike S protein ORF3 ORFs 3a and 3b small envelop E or 3c protein membrane M protein ORF X ORF5 ORFs 5a and 5b nucleocapsid N protein 3 UTR poly A


id: cord-286473-sl5zy8nj
type: CHEBI
entity:
  protein membrane M protein ORF5 ORFs X 5a 5b nucleocapsid N protein 3 UTR poly A TCoV genome structure and sequence


id: cord-275413-e2rhioty
type: GGP
entity:
  fetuses 1 2 3 12 4 9 4 11 4 13 in Fig 1 The mechanism for fetal pathology remains unclear but the results suggest that the source pathology is likely result of the infection of tissues on the maternal side


id: cord-295187-konm26x5
type: PROTEIN
entity:
  virulent canine coronavirus BGF strain MEGA4 Molecular Evolutionary Genetics Analysis MEGA software version 4 0


id: cord-275016-ij5yaqkx
type: CHEMICAL
entity:
  N terminal His tagged 3CD fragment containing the Ala mutation of active site Cys139 of the 3C like protease Fig 1B However this protein tended to aggregate at higher pH


id: cord-260107-gqbtkf0x
type: PROTEIN
entity:
  N D b ND ND ND ND ND ND ND ORF1a 12 354 ND ND ND ND ND ND ND ND ORF1ab 20 345 N D ND ND ND ND ND ND ND S 4 161 21448 A A A A C C C 272 K K K K T T T 21756 C T T T T T T


id: cord-256343-dtfw8o4g
type: DNA
entity:
  G gallus genes lung surfactant protein A intestinal cholecystokinin oviduct ovomucin alpha subunit kidney vitamin D receptor


id: cord-309205-l8vjtrjq
type: DISEASE
entity:
  critically distinguishing feature between the two feline coronavirus FCoV pathotypes feline enteric coronavirus FECV


id: cord-320331-wtxja5i9
type: CELL_TYPE
entity:
  esophageal epithelial cells enterocytes male reproductive cells type II lung alveolar epithelial cells renal tubules ductal cells bladder urothelial cells endothelial cells


id: cord-320331-wtxja5i9
type: PROTEIN
entity:
  growth factor 2 receptor IGF2R angiotensinogen AGT epidermal growth factor receptor EGFR matrix metalloendopeptidase MME alanyl aminopeptidase


id: cord-320331-wtxja5i9
type: GGP
entity:
  growth factor 2 receptor IGF2R angiotensinogen AGT epidermal growth factor receptor EGFR matrix metalloendopeptidase MME alanyl aminopeptidase ANPEP


id: cord-320331-wtxja5i9
type: WORK_OF_ART
entity:
  The Effects of ARBs ACEis and Statins on Clinical Outcomes of COVID 19 Infection Among Nursing Home Residents


id: cord-329183-s0zrvn9o
type: DNA
entity:
  rice dwarf virus RDV genus Phytoreovirus 29 identity 55 similarity 55 similarity amino acids 1 70 of RDV P3


id: cord-268010-1m5h3krw
type: DNA
entity:
  5 untranslated region open reading frame 1a 1b ORF1a 1b S E M nonstructural protein 6 NS6 N nonstructural protein 7 NS7 and 3 UTR


id: cord-288253-wqrhiq08
type: ORG
entity:
  the Technology Development Program for Agriculture and Forestry Ministry for Food Agriculture Forestry


id: cord-020087-gs0pc6ee
type: CELL_LINE
entity:
  cell clones 218 USA Genetic control of host resistance to porcine reproductive and respiratory syndrome virus PRRSV infection Porcine reproductive and respiratory syndrome virus PRRSV


id: cord-280643-n8qjorqk
type: DNA
entity:
  siRNA target sites 1 HBS 1 siRNA 2 HBS 2 siRNA 3 HBS 3 siRNA 4 HBS 4 siRNA 5 HBS 5 siRNA 6 HBX 1 siRNA 7 HBX 2 siRNA 8 HBX 3 siRNA c Diagram


id: cord-332075-gxmae2rs
type: DNA
entity:
  5 GCGCGTTTAAACTTAAGAAAAAATACGGGTAGAAGCCGCCACCAT GGCAGAGGGAGGAGGCGG 3 and 5 GCGCGTTTAAACTTACAGAT TTTGAGTTAGATATC 3


id: cord-304137-vxqkztio
type: GGP
entity:
  p38 c Jun N terminal mitogen activated protein kinase pathways and activates transcription factor AP 1


id: cord-335706-lopcb77c
type: CHEMICAL
entity:
  carboxy terminal beta strand of the porcine reproductive and respiratory syndrome virus nucleocapsid protein The 2b


id: cord-345999-iiw4cs8p
type: PROTEIN
entity:
  Spike Protein S Yi 2004 4 Myricetin 2 5 3 0 μM Helicase Yu 2012 5 Scutellarein 0 4 1 24 μM Helicase Yu 2012 6 Baicalin 2 24mM Angiotensin converting enzyme 2 ACE2 receptor


id: cord-345999-iiw4cs8p
type: CHEMICAL
entity:
  Saikosaponin B2 1 7 0 1 μmol L 55 Saikosaponin C 19 9 0 1 μmol L 56 Saikosaponin D 0 02 0 001μmol L 57 R


id: cord-279969-5nlmljcw
type: PROTEIN
entity:
  N U39295 P U22110 M X58639 F Y14294 APV B N U39296 P AF325443 M U37586 F Y14293 APV C N AF176590 P AF176591 M AF072682 F AF187152 PVM N D10331 P U092942 M U66893 F D11128 hMPV Netherlands isolate 00 1 NLD00 1 N AF371365 P AF371366 M and F AF371367 The hMPV sequences


id: cord-279969-5nlmljcw
type: DNA
entity:
  human parainfluenza virus type 3 patterns of amino acid sequence homology among paramyxovirus proteins A


id: cord-279969-5nlmljcw
type: DISEASE
entity:
  respiratory syncytial viral genes Cloning and sequencing of the matrix protein M gene of turkey rhinotracheitis


id: cord-279849-zzkliu76
type: PROTEIN
entity:
  Autographa californica nuclear polyhedrosis virus Friesen and Nissen 1990 and reticuloendotheliosis virus


id: cord-346264-hnwgzt6v
type: PROTEIN
entity:
  nonstructural proteins NS1 NS2 NS3 putative NTPase NS4 NS5 VPg NS6 protease NS7 RNA dependent RNA polymerase RdRp


id: cord-347270-x05tfkgx
type: DNA
entity:
  Betacoronavirus 1species 5 UTR nt 1 143 ORF1ab nt 144 21427 ORF2 nt 21437 22273 HE gene nt 22285 23559 S gene nt 23574 27665 E gene nt 28355 28609 M gene nt 28624 29316 N gene nt 29326 30672 and 3 UTR nt 30673 30868


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


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


id: cord-284866-66azyje4
type: DNA
entity:
  Escherichia coli Bacillus subtilis Saccharomyces cerevisiae Schizosaccharomyces pombe Drosophila melanogaster


id: cord-294764-v28wbrqp
type: DISEASE
entity:
  genogroups designated GI GVII based on phylogenetic analysis of the capsid gene Vinje 2015 Genogroups GI GII and GIV infect humans and cause acute gastroenteritis Norovirus


id: cord-294764-v28wbrqp
type: DISEASE
entity:
  influenza A virus polymerase Biochemical evaluation of the inhibition properties of favipiravir and 2 C methyl cytidine triphosphates


id: cord-285180-32bxx94u
type: CHEMICAL
entity:
  PDCoV N gene expression plasmid pFB Neo PDCoV N myc His that produces recombinant N protein The retrovirus gene transfer system Stratagene


id: cord-344084-z4t2wkgk
type: DISEASE
entity:
  rheumatologic dermatologic ophthalmologic renal pulmonary neuropsychiatric cardiovascular and hematologic manifestations


id: cord-312848-vbadg8ki
type: DNA
entity:
  follows 1st upstream primer 5 ATGTTTTTGATACTTTTAATTTCC 3 1 24 1st downstream primer 5 ACACCAGTAGATGGTGCTAT 3 901 920 2nd upstream primer 5


id: cord-312848-vbadg8ki
type: ORG
entity:
  the Technology Development Program for Agriculture and Forestry Ministry of Agriculture and Forestry Republic


id: cord-346104-18x8u2oe
type: DNA
entity:
  human rectal tumor HrT 18G cells Marbin Darby Canine Kidney MDCK Vero Maru Vero Crandell Feline Kidney CRFK cells Porcine Kidney 15 PK 15 and Rabbit Kidney 13B RK 13B cells


id: cord-346104-18x8u2oe
type: GGP
entity:
  Percavirus Phocid herpesvirus 2 EHV 2 Equid gammaherpesvirus 2 HHV 8 human herpesvirus type 8 RHV 1 Gorilla rhadinovirus 1 isolate UrHV 1 Ursid gammaherpesvirus 1 B1 amplicon


id: cord-346104-18x8u2oe
type: CHEMICAL
entity:
  Rhadinovirus Fig 6 The old classification of Gammaherpesvirinae consists of 2 genera Lymphocryptovirus


id: cord-314415-yr0uxok2
type: DNA
entity:
  bovine enterovirus 8785 reads bovine kobuvirus 549 reads bovine herpesvirus 1 199 reads nebovirus 107 reads bovine coronavirus 50 reads bovine adenovirus type 3 5 reads


id: cord-263178-lvxxdvas
type: PROTEIN
entity:
  rHVR I II 7 10 0 10 10 10 6 10 4 10 0 10 0 10 0 10 3 10 5 10 7 10 10 10 7 10 10 10 10 10 10 10 10 10 rHVR I III 7 10 1 10 10 10 7 9 2 9 0 9 0 9 0 10 2 10 4 10 6 10 10 10 6 10 9 9 9 9 9 9 9 9 rHVR II III 8 10 2 10 10 10 6 8 1 8 0 8 0 8 0 10 1 10 3 10 6 10 10 10 7 10 8 8 8 8 8 8 8


id: cord-263178-lvxxdvas
type: PROTEIN
entity:
  rHVR I II III 7 10 0 10 10 10 6 10 5 10 0 10 0 10 0 10 2 10 5 10 7 10 10 10 8 10 10 10 10 10 10 10 10 10 Beaudette 9 10 1 10 10 10 4 9 4 9 1 9 0 9 0 10 2 10 4 10 6 10 10 10 6 10 9 9 9 9 9 9 9 9 ck CH LDL 091022 2 5 c 0 5 5 5 3 5 2 5 0 5 0 5 0 10 5 6 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 PBS 10 10 3 10 10 10 8 9 3 7 0 7 0 7 0 10 0 10 0 10 0 10 0 10 3 10 4 9 5 7 7 7 7 7 a


id: cord-302083-9q1i20o6
type: WORK_OF_ART
entity:
  Neutralizing Antibody Response in Mammary Secretions Reactivity of Porcine Epidemic Diarrhea Virus Structural Proteins to Antibodies against Porcine Enteric Coronaviruses Diagnostic Implications


id: cord-302083-9q1i20o6
type: WORK_OF_ART
entity:
  Swine The Role of Non animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine A Review of Scientific Literature Frontiers


id: cord-302083-9q1i20o6
type: ORG
entity:
  Immunoglobulin Transporting Receptors Are Potential Targets for the Immunity Enhancement and Generation of Mammary Gland Bioreactor


# bib

id: cord-020087-gs0pc6ee
title: Cumulative Contents for 2010
author: nan
date: 2010-11-18
txt: ./txt/cord-020087-gs0pc6ee.txt
cache: ./cache/cord-020087-gs0pc6ee.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134101/
doi: 10.1016/s0168-1702(10)00397-7
abstract: nan
summary:
  Myristoylation of the small envelope protein of porcine reproductive and respiratory syndrome virus is non-essential for virus infectivity but promotes its growth 294 Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing Hikichi (Japan) The 126-and/or 183-kDa replicases or their coding regions are responsible both for inefficient local and for systemic movements of Paprika mild mottle virus Japanese strain in tomato plants USA) Genetic control of host resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection Porcine reproductive and respiratory syndrome virus (PRRSV) in serum and oral fluid samples from individual boars: Will oral fluid replace serum for PRRSV surveillance USA) Use of a production region model to assess the efficacy of various air filtration systems for preventing airborne transmission of porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae: Results from a 2-year study 177 Morrison (USA) Control and elimination of porcine reproductive and respiratory syndrome virus 185 Cumulative Author Index for


id: cord-020097-eh5deunk
title: Cumulative Author Index for 2006 (Volumes 115–122)
author: nan
date: 2006-10-27
txt: ./txt/cord-020097-eh5deunk.txt
cache: ./cache/cord-020097-eh5deunk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134138/
doi: 10.1016/s0168-1702(06)00318-2
abstract: nan
summary:
  Modulation of PKR activity in cells infected by bovine viral diarrhea virus Complete genome analysis of RFLP 184 isolates of porcine reproductive and respiratory syndrome virus Phylogenetic analysis of the gag region encoding the matrix protein of small ruminant lentiviruses: Comparative analysis and molecular epidemiological applications TATAbinding protein and TBP-associated factors during herpes simplex virus type 1 infection: Localization at viral DNA replication sites Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein Efficient inhibition of hepatitis B virus replication by small interfering RNAs targeted to the viral X gene in mice Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein A deletion and point mutation study of the human papillomavirus type 16 major capsid gene Sequencing and comparative analysis of a pig bovine viral diarrhea virus genome Antigenic structure analysis of glycosylated protein 3 of porcine reproductive and respiratory syndrome virus


id: cord-020101-5rib7pe8
title: Cumulative Author Index for 2008
author: nan
date: 2008-11-17
txt: ./txt/cord-020101-5rib7pe8.txt
cache: ./cache/cord-020101-5rib7pe8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134142/
doi: 10.1016/s0168-1702(08)00367-5
abstract: nan
summary:
  Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of Increase in proto-oncogene mRNA transcript levels in bovine lymphoid cells infected with a cytopathic type 2 bovine viral diarrhea virus Complete genome sequence analysis of dengue virus type 2 isolated in Modulation of hepatitis B virus replication by expression of polymerasesurface fusion protein through splicing: Implications for viral persistence Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors


id: cord-252048-ftbjsoup
author: McKinley, Enid T.
date: 2011-04-22
txt: ./txt/cord-252048-ftbjsoup.txt
cache: ./cache/cord-252048-ftbjsoup.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2011.04.006
doi: 10.1016/j.virusres.2011.04.006
summary:
  The full-length genomes of 11 infectious bronchitis virus (IBV) field isolates from three different types of the virus; Massachusetts (Mass), Connecticut (Conn) and California (CAL) isolated over a 41, 25 and 8 year period respectively, were sequenced and analyzed to determine the mutation rates and level of polymorphisms across the genome. The genetic data also identified a recombinant IBV isolate with 7 breakpoints distributed across the entire genome suggesting that viruses within the same serotype can have a high degree of genetic variability outside of the spike gene. The objective of this study was to determine the levels of polymorphism across the entire genome of IBV isolates with similar spike genes and to examine the mutation rates for viruses with and without vaccine selection pressure.

title:
  Attenuated live vaccine usage affects accurate measures of virus diversity and mutation rates in avian coronavirus infectious bronchitis virus

abstract:
  The full-length genomes of 11 infectious bronchitis virus (IBV) field isolates from three different types of the virus; Massachusetts (Mass), Connecticut (Conn) and California (CAL) isolated over a 41, 25 and 8 year period respectively, were sequenced and analyzed to determine the mutation rates and level of polymorphisms across the genome. Positive selection was not detected and mutation rates ranged from 10(−4) to 10(−6) substitutions/site/year for Mass and Conn IBV types where attenuated live vaccines are routinely used to control the disease. In contrast, for CAL type viruses, for which no vaccine exists, positive selection was detected and mutation rates were 10 fold higher ranging from 10(−2) to 10(−3) substitutions/site/year. Lower levels of genetic diversity among the Mass and Conn viruses as well as sequence similarities with vaccine virus genomes suggest that the origin of the Mass and all but one of the Conn viruses was likely vaccine virus that had been circulating in the field for an unknown but apparently short period of time. The genetic data also identified a recombinant IBV isolate with 7 breakpoints distributed across the entire genome suggesting that viruses within the same serotype can have a high degree of genetic variability outside of the spike gene. These data are important because inaccurate measures of genetic diversity and mutation rates could lead to underestimates of the ability of IBV to change and potentially emerge to cause disease.


id: cord-255857-y9wjp0aj
author: Yuan, Shishan
date: 2001-11-05
txt: ./txt/cord-255857-y9wjp0aj.txt
cache: ./cache/cord-255857-y9wjp0aj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/11551659/
doi: 10.1016/s0168-1702(01)00295-7
summary:
  Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. However, the cluster of amino acid mutations located near the carboxyl terminal end suggests that the replicase region was altered during passage to result in a more fit virus for replication in cell culture, as evidenced by the in vitro one-step growth curve comparison shown in Fig. 4 . Sequence analysis of strains VR-2332 and RespPRRS indicated that there were 15 nucleotide changes in this region, and all but one of which resulted in amino acid alterations. Attenuation can result from changes in many areas of viral genomes and the 41 nucleotide mutations described include alterations in several key PRRSV regions.

title:
  Erratum to “Complete genome comparison of porcine reproductive and respiratory syndrome virus parental and attenuated strains”

abstract:
  Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. Of the 41 nucleotide changes, 12 resulted in conservative changes and 18 produced non-conservative changes. The results suggest that key amino acids in ORF1 may contribute to the phenotype of RespPRRS, which includes increased growth rate on MA-104 cells and decreased virulence in swine. The results provide a genetic basis for future manipulation of a PRRSV reverse genetics system.


id: cord-256343-dtfw8o4g
author: Brandão, Paulo Eduardo
date: 2013-12-26
txt: ./txt/cord-256343-dtfw8o4g.txt
cache: ./cache/cord-256343-dtfw8o4g.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170213003250
doi: 10.1016/j.virusres.2013.09.033
summary:
  Neighbor-joining distance tree for the relative synonymous codon usage (RSCU) for the Avian coronavirus spike (S), nucleocapsid (N), non-structural protein 2 (NSP2) and papain-like protease (PL pro ) genes and the Gallus gallus beta-actin, lung surfactant protein A (SFTPA1, gray background), intestinal cholecystokinin (CCK), oviduct ovomucin alpha subunit (OSA) and kidney vitamin D receptor genes. The mean number of amino acid residues in the sequences used for this study from the Avian coronavirus spike (S), nucleocapsid (N), non-structural protein 2 (NSP2) and papain-like protease (PL pro ) genes coded by a preferred codon and the preferred codon for each aa in the Gallus gallus beta-actin (B-act), lung surfactant protein A (SFTPA1), intestinal cholecystokinin (CCK), oviduct ovomucin alpha subunit (Ovo) and kidney vitamin D receptor (ViTD rec) genes.

title:
  The evolution of codon usage in structural and non-structural viral genes: The case of Avian coronavirus and its natural host Gallus gallus

abstract:
  To assess the codon evolution in virus–host systems, Avian coronavirus and its natural host Gallus gallus were used as a model. Codon usage (CU) was measured for the viral spike (S), nucleocapsid (N), nonstructural protein 2 (NSP2) and papain-like protease (PL(pro)) genes from a diverse set of A. coronavirus lineages and for G. gallus genes (lung surfactant protein A, intestinal cholecystokinin, oviduct ovomucin alpha subunit, kidney vitamin D receptor and the ubiquitary beta-actin) for different A. coronavirus replicating sites. Relative synonymous codon usage (RSCU) trees accommodating all virus and host genes in a single topology showed a higher proximity of A. coronavirus CU to the respiratory tract for all genes. The codon adaptation index (CAI) showed a lower adaptation of S to G. gallus compared to NSP2, PL(pro) and N. The effective number of codons (Nc) and GC(3%) revealed that natural selection and genetic drift are the evolutionary forces driving the codon usage evolution of both A. coronavirus and G. gallus regardless of the gene being considered. The spike gene showed only one 100% conserved amino acid position coded by an A. coronavirus preferred codon, a significantly low number when compared to the three other genes (p < 0.0001). Virus CU evolves independently for each gene in a manner predicted by the protein function, with a balance between natural selection and mutation pressure, giving further molecular basis for the viruses’ ability to exploit the host's cellular environment in a concerted virus–host molecular evolution.


id: cord-257487-xanqvdhn
title: Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506
author: Carbajo-Lozoya, Javier
date: 2012-02-10
txt: ./txt/cord-257487-xanqvdhn.txt
cache: ./cache/cord-257487-xanqvdhn.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2012.02.002
doi: 10.1016/j.virusres.2012.02.002
summary:
  Knockdown of the cellular FK506-binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth. Here we demonstrate that the drug FK506 (Tacrolimus) inhibited strongly the growth of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E at low, non-cytotoxic concentrations in cell culture. Knockdown of the cellular FK506binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth. To examine whether FK506 exerts an inhibitory activity on other human coronaviruses, CaCo2 cells were infected with HCoV-NL63 at MOI = 0.004 (Herzog et al., 2008) in the presence of increasing inhibitor concentrations. In order to examine whether the cellular FK506-binding proteins FKBP1A and FKBP1B are required for virus replication, CaCo2 knockdown cell lines were established using lentiviral expression of shRNA (Sirion GmbH, Martinsried, Germany).

abstract:
  Recent research has shown that Coronavirus (CoV) replication depends on active immunophilin pathways. Here we demonstrate that the drug FK506 (Tacrolimus) inhibited strongly the growth of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E at low, non-cytotoxic concentrations in cell culture. As shown by plaque titration, qPCR, Luciferase- and green fluorescent protein (GFP) reporter gene expression, replication was diminished by several orders of magnitude. Knockdown of the cellular FK506-binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth.


id: cord-257715-pbcr81qm
title: Molecular characterization of a new PToV strain. Evolutionary implications
author: Pignatelli, J.
date: 2009-03-20
txt: ./txt/cord-257715-pbcr81qm.txt
cache: ./cache/cord-257715-pbcr81qm.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2009.02.019
doi: 10.1016/j.virusres.2009.02.019
summary:
  Thus, there have been a few reports where indirect ELISA using partially purified BToV or BEV particles were used for torovirus serodiagnosis, but purification procedures are not affordable by all laboratories and, in addition, this assay would also provide low sensitivity for detection of antibodies to human and porcine toroviruses (Brown et al., 1987) . Lack of cross-reactivity between PToV and antibodies to other related viruses infecting pigs was confirmed by ELISA, Western blot and virus neutralization tests using ␣PRRSV, ␣PRCV, and ␣BRES serum samples, purified PToV N protein or BEV particles as toroviral antigens, and purified PRRSV and TGEV virions as related viruses (data not shown). In order to evaluate the potential use of the PToV-N protein as antigen for diagnostic ELISA to detect antibodies against porcine torovirus, 45 serum samples were collected from three Spanish farms located in Galicia, Navarra and Aragon and were analyzed by ELISA, virus neutralization assay and/or Western blot. Recombinant PToV-BRES-N protein was used to develop an ELISA assay to detect antibodies against torovirus in swine serum samples.

abstract:
  Toroviruses are emergent viruses, belonging to the Nidovirales order, that remain mostly ignored, despite they are able to infect different species of domestic animals and humans, causing enteric diseases and diarrhea. Thus far, only five variants of porcine torovirus (PToV) have been identified. In this report we describe the identification and partial characterization of a new strain of porcine torovirus (PToV-BRES) that was detected by RT-PCR in a swine faecal specimen from a farm in Brescia (Italy). The complete genes coding for the nucleocapsid (N), hemagglutinin-esterase (HE) and membrane (M) proteins were amplified, and sequence analysis showed that PToV-BRES is a new PToV strain that, based on the HE gene sequence, is phylogenetically related to P4 strain, that was up to now the only member of a distinct PToV lineage. The nucleocapsid protein from PToV-BRES was expressed in insect cells as a his-tagged protein, purified by affinity chromatography and used to develop an ELISA method to detect antibodies against PToV. This assay was evaluated using a serum collection including 45 samples from three commercial farms from Spain. High antibody prevalence against PToV was observed in the three farms, both in adult animals and in piglets, which could suggest that PToV might be endemic in Spanish porcine population. The ELISA method developed in this work could be useful in future epidemiological surveys about toroviruses.


id: cord-258294-ny3xrjzc
author: Gao, Xiang
date: 2020-04-02
txt: ./txt/cord-258294-ny3xrjzc.txt
cache: ./cache/cord-258294-ny3xrjzc.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170220300010?v=s5
doi: 10.1016/j.virusres.2020.197955
summary:
  Compared with nonvaccinated pigs, conventional weaned pigs given the inactivated vaccine developed a potent humoral immune response and showed no clinical signs or viral shedding after challenge, indicating a potent protective effect of the vaccine against PDCoV infection. Piglets in the infection group and mock control group were separately inoculated with 3 ml of MEM containing 1.0×10 4 TCID50 of the cell culture-adapted PDCoV strain CH/XJYN/2016-P6. To determine a standardized and validated dose for the subsequent pig challenge experiments, the median pig diarrhea dose (PDD50) of P6 of the cell culture-adapted PDCoV strain, CH/XJYN/2016, was determined by using conventional weaned pigs as described in our previous study (Zhang et al., 2019a) . Therefore, the infectious titer (PDD50) of PDCoV in two-month-old conventional pigs and the protection efficacity of an inactivated vaccine based on the cell-adapted strain CH/XJYN/2016 were determined for the first time in the present study.

title:
  Characterization, Pathogenicity and Protective efficacy of a Cell Culture-Derived Porcine Deltacoronavirus

abstract:
  Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes acute diarrhea, vomiting, dehydration and mortality in neonatal piglets, resulting in significant economic losses to the pig industry. However, there is currently little information on vaccine studies and commercially available vaccines for PDCoV. Hence, herein, a PDCoV strain, CH/XJYN/2016, was successfully isolated and serially propagated in vitro, and its biological characteristics were determined. Compared to that of previously reported and recently isolated PDCoV strains from China and the United States, the S gene of the CH/XJYN/2016 strain contains novel mutations. Infection studies revealed that CH/XJYN/2016 is pathogenic to suckling piglets and conventional weaned pigs. In addition, the median pig diarrhea dose (PDD(50)) of PDCoV in conventional weaned pigs was determined (2.0 log(10)PDD(50)/3 mL). Furthermore, an inactivated cell-adapted CH/XJYN/2016-based vaccine candidate was developed with different adjuvants. Compared with nonvaccinated pigs, conventional weaned pigs given the inactivated vaccine developed a potent humoral immune response and showed no clinical signs or viral shedding after challenge, indicating a potent protective effect of the vaccine against PDCoV infection. Therefore, the PDCoV vaccine developed in this study is a promising vaccine candidate that can be used for the control of PDCoV infection in pigs.


id: cord-258546-1tf5ggfo
title: New emergence pattern with variant porcine epidemic diarrhea viruses, South Korea, 2012–2015
author: Chung, Hee-Chun
date: 2016-12-02
txt: ./txt/cord-258546-1tf5ggfo.txt
cache: ./cache/cord-258546-1tf5ggfo.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2016.06.013
doi: 10.1016/j.virusres.2016.06.013
summary:
  Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014–2015 year. PED outbreaks re-occurred in Korea in 2013, however, it was demonstrated that the emerging PEDVs were not variants of old Korean isolates or attenuated vaccine strains (Chung et al., 2015) . This study tested whether PEDV isolated recently was crossed neutralized by serum of pigs which were vaccinated with Korean PED oral vaccine (Attenuated DR13 strain, Green Cross Veterinary Product Co., Ltd., Yong-In, Korea). Comparative genome analysis and molecular epidemiology of the reemerging porcine epidemic diarrhea virus strains isolated in Korea ISolation of porcine epidemic diarrhea virus during outbreaks in South Korea Isolation of porcine epidemic diarrhea virus (PEDV) in Korea Heterogeneity in spike protein genes of porcine epidemic diarrhea viruses isolated in Korea

abstract:
  Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014–2015 year. This study analyzed a large collection of the Spike protein coding gene to infer the spatial-temporal diffusion history of PEDV. The studying results suggested that PEDVs in Korea belonged to different genogroups. While classical G1 was continuingly circulating between provinces of Korea, the pandemic G2a were recently introduced from China and USA. By the application of Bayesian phylogeographical analysis, this study demonstrated the spatial-temporal transmission of PEDVs within Korea. Of the recent emerged G2a viruses, J3142 strains showed potential recombination breakpoint (376–2,143nt) of S1 gene between KNU1303_Korea strain_G2a (KJ451046) and 45RWVCF0712_Thailand strain_G2b (KF724935). The pandemic G2a virus was partial neutralized by the antibodies invoked by the G1- based PED vaccine virus.


id: cord-259044-mubjm22l
author: Weng, Jing-Ru
date: 2019-09-24
txt: ./txt/cord-259044-mubjm22l.txt
cache: ./cache/cord-259044-mubjm22l.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170219304198
doi: 10.1016/j.virusres.2019.197767
summary:
  The study indicated the inhibitory activity of Sambucus FormosanaNakai extract and its phenolic acid constituents on HCoV-NL63 induced cytopathic effect, virus yield, and the early stage of HCoV-NL63 replication in concentration-dependent and cell-type independent manners. LLC-MK2 cells (3 × 10 4 cells/well) were cultured in the 96-well plates overnight, quintuplicate treated with Sambucus Formosana Nakai stem ethanol extract or its phenolic acid constituents (caffeic acid, chlorogenic acid, coumaric acid, ferulic acid, and gallic acid) for 2 days, and then incubated with 0.5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) for additional 4 h. For minimizing the antiviral effect of indicated agents in the cells, 100 μl (near 200 pfu HCoV-NL63) of the 10000-fold dilution from the mixtures of virus and the extract or phenolic acids was added to the MK2 cell monolayer in the 6-well plate to determining the residual viral infectivity using the plaque assay described above. To examine the antiviral mechanism of caffeic acid and chlorogenic acid against HCoV-NL63, the assays of plaque formation, virucidal activity and virus attachment were subsequently performed (Fig. 5 , Table 1 ).

title:
  Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63

abstract:
  Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia. Recently, a severe respiratory illness outbreak of HCoV-NL63 has been reported in a long-term care facility. Sambucus FormosanaNakai, a species of elderberry, is a traditional medicinal herb with anti-inflammatory and antiviral potential. The study investigated the antiviral activity of Sambucus FormosanaNakai stem ethanol extract and some phenolic acid constituents against HCoV-NL63. The extract was less cytotoxic and concentration-dependently increased anti-HCoV-NL63 activities, including cytopathicity, sub-G1 fraction, virus yield (IC50 = 1.17 μg/ml), plaque formation (IC50 = 4.67 μg/ml) and virus attachment (IC50 = 15.75 μg/ml). Among the phenolic acid constituents in Sambucus FormosanaNakai extract, caffeic acid, chlorogenic acid and gallic acid sustained the anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid (IC(50) = 3.54 μM) > chlorogenic acid (IC(50) = 43.45 μM) > coumaric acid (IC(50) = 71.48 μM). Caffeic acid significantly inhibited the replication of HCoV-NL63 in a cell-type independent manner, and specifically blocked virus attachment (IC(50) = 8.1 μM). Therefore, the results revealed that Sambucus Formosana Nakai stem ethanol extract displayed the strong anti-HCoV-NL63 potential; caffeic acid could be the vital component with anti-HCoV-NL63 activity. The finding could be helpful for developing antivirals against HCoV-NL63.


id: cord-259671-7de21oaq
title: RNA structure analysis of alphacoronavirus terminal genome regions
author: Madhugiri, Ramakanth
date: 2014-12-19
txt: ./txt/cord-259671-7de21oaq.txt
cache: ./cache/cord-259671-7de21oaq.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170214004055
doi: 10.1016/j.virusres.2014.10.001
summary:
  Overall, the conservation pattern identified for 5′ and 3′-terminal RNA structural elements in the genomes of alphaand betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements. Other internal cis-acting elements include specific RNA signals required for genome packing, which have been characterized in a small number of coronaviruses Escors et al., 2003; Morales et al., 2013; Penzes et al., 1994) , and a complex RNA pseudoknot structure located in the ORF1a-ORF1b overlap region that mediates a (−1) ribosomal frameshift event and thus controls the expression of the second large ORF on the coronavirus genome RNA (ORF1b) (Brierley et al., 1987 (Brierley et al., , 1989 de Haan et al., 2002; Namy et al., 2006) .

abstract:
  Coronavirus genome replication is mediated by a multi-subunit protein complex that is comprised of more than a dozen virally encoded and several cellular proteins. Interactions of the viral replicase complex with cis-acting RNA elements located in the 5′ and 3′-terminal genome regions ensure the specific replication of viral RNA. Over the past years, boundaries and structures of cis-acting RNA elements required for coronavirus genome replication have been extensively characterized in betacoronaviruses and, to a lesser extent, other coronavirus genera. Here, we review our current understanding of coronavirus cis-acting elements located in the terminal genome regions and use a combination of bioinformatic and RNA structure probing studies to identify and characterize putative cis-acting RNA elements in alphacoronaviruses. The study suggests significant RNA structure conservation among members of the genus Alphacoronavirus but also across genus boundaries. Overall, the conservation pattern identified for 5′ and 3′-terminal RNA structural elements in the genomes of alpha- and betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements.


id: cord-259935-xyo2pe4g
author: Wang, Ching-Ying
date: 2017-05-02
txt: ./txt/cord-259935-xyo2pe4g.txt
cache: ./cache/cord-259935-xyo2pe4g.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28414040/
doi: 10.1016/j.virusres.2017.04.008
summary:
  To examine the association of SARS-CoV PLpro-induced TGF-β1 production with the collagen up-regulation, A549 lung epithelial cells transiently transfected with pcDNA3.1 and pSARS-PLpro were analyzed the production of TGF-β1 and type I collagen using Western blot, realtime RT-PCR and Sirius red staining assays (Fig. 1) . To examine whether SMAD-dependent pathways involve in TGF-β1mediated up-regulation of Type I collagen in response SARS-CoV PLpro, subcellular localization of receptor-regulated SMAD3 and inhibitory SMAD7 in transfected cells were detected using the immunofluorescent and DAPI staining (Fig. 4) . To examine the possible pathways involved in TGF-β1-dependent up-regulation of Type I collagen by SARS-CoV PLpro, the profiles of ubiquitin-conjugated proteins in transfected cells with vector control and pSARS-PLpro were determined using immune-precipitation and nanoLC-MS/MS. Subcellular localization analysis demonstrated that SMAD3 was predominant in cytoplasmic, but not in the nucleus in transfected cells with pSARS-PLpro compared to vector control (Fig. 4) , revealing that canonical Smad-dependent signaling pathway was not involved in PLpro-induced TGF-β1-dependent upregulation of Type I collagen.

title:
  SARS coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-β1 signaling

abstract:
  SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro. Comprehensive analysis of ubiquitin-conjugated proteins using immunoprecipitation and nanoLC–MS/MS indicated that SARS-CoV PLpro caused the change in the ubiquitination profile of Rho GTPase family proteins, in which linked with the increase of Rho-like GTPase family proteins. Moreover, selective inhibitors TGF-βRI and STAT6 (AS1517499) ascertained that STAT6 activation was required for PLpro-induced TGF-β1-dependent up-regulation of Type I collagen in human lung epithelial cells. The results showed that SARS-CoV PLpro stimulated TGF-β1-dependent expression of Type I collagen via activating STAT6 pathway.


id: cord-260107-gqbtkf0x
title: Isolation and characterization of a Korean porcine epidemic diarrhea virus strain KNU-141112
author: Lee, Sunhee
date: 2015-10-02
txt: ./txt/cord-260107-gqbtkf0x.txt
cache: ./cache/cord-260107-gqbtkf0x.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170215300149
doi: 10.1016/j.virusres.2015.07.010
summary:
  In the present study, one Korean PEDV strain, KOR/KNU-141112/2014, was successfully isolated and serially propagated in Vero cells for over 30 passages. Our genomic analyses indicated that the Korean isolate KNU-141112 is genetically stable during the first 30 passages in cell culture and is grouped within subgroup G2b together with the recent re-emergent Korean strains. Our data indicated that KNU-141112 isolate is relatively stable during the first 30 passages in cell culture and is classified into subgroup G2b that includes PEDV strains responsible for recent severe outbreaks in Korea and the US. Although virus isolation in cell culture from clinical samples of naturally or experimentally infected pigs is fastidious, recent studies reported the successful isolation and propagation of several US original PEDV strains using Vero cells (Chen et al., 2014; Oka et al., 2014) . Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene

abstract:
  Severe outbreaks of porcine epidemic diarrhea virus (PEDV) have re-emerged in Korea and rapidly swept across the country, causing tremendous economic losses to producers and customers. Despite the availability of PEDV vaccines in the domestic market, the disease continues to plague the Korean pork industry, raising issues regarding their protective efficacy and new vaccine development. Therefore, PEDV isolation in cell culture is urgently needed to develop efficacious vaccines and diagnostic assays and to conduct further studies on the virus biology. In the present study, one Korean PEDV strain, KOR/KNU-141112/2014, was successfully isolated and serially propagated in Vero cells for over 30 passages. The in vitro and in vivo characteristics of the Korean PEDV isolate were investigated. Virus production in cell culture was confirmed by cytopathology, immunofluorescence, and real-time RT-PCR. The infectious virus titers of the viruses during the first 30 passages ranged from 10(5.1) to 10(8.2) TCID(50) per ml. The inactivated KNU-141112 virus was found to mediate potent neutralizing antibody responses in immunized guinea pigs. Animal studies showed that KNU-141112 virus causes severe diarrhea and vomiting, fecal shedding, and acute atrophic enteritis, indicating that strain KNU-141112 is highly enteropathogenic in the natural host. In addition, the entire genomes or complete S genes of KNU-141112 viruses at selected cell culture passages were sequenced to assess the genetic stability and relatedness. Our genomic analyses indicated that the Korean isolate KNU-141112 is genetically stable during the first 30 passages in cell culture and is grouped within subgroup G2b together with the recent re-emergent Korean strains.


id: cord-260422-z22t57ju
author: Godet, Julien
date: 2012-06-26
txt: ./txt/cord-260422-z22t57ju.txt
cache: ./cache/cord-260422-z22t57ju.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170212002183
doi: 10.1016/j.virusres.2012.06.021
summary:
  Today''s view is that RNA chaperones are nucleic acid binding proteins present in all living organisms, including viruses, where they Abbreviations: HIV-1, human immunodeficiency virus-type I; NCp7, nucleocapsid protein of HIV-1; ZF, zinc finger; NA, nucleic acid; TAR, transactivation response element; PBS, primer binding site; AA, amino acids. The substantial nucleic acid chaperone properties exhibited by Tat may account for its ability to promote the annealing of the primer tRNA to the viral RNA (Kameoka et al., 2002) and intervene in the first strand transfer (Boudier et al., 2010) and by this way, to stimulate RTion as does NCp7 (Harrich et al., 1997; Ulich et al., 1999; Apolloni et al., 2007) . Human immunodeficiency virus Type 1 nucleocapsid protein (NCp7) directs specific initiation of minusstrand DNA synthesis primed by human tRNA(Lys3) in vitro: studies of viral RNA molecules mutated in regions that flank the primer binding site

title:
  Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1

abstract:
  RNA chaperones are proteins able to rearrange nucleic acid structures towards their most stable conformations. In retroviruses, the reverse transcription of the viral RNA requires multiple and complex nucleic acid rearrangements that need to be chaperoned. HIV-1 has evolved different viral-encoded proteins with chaperone activity, notably Tat and the well described nucleocapsid protein NCp7. We propose here an overview of the recent reports that examine and compare the nucleic acid chaperone properties of Tat and NCp7 during reverse transcription to illustrate the variety of mechanisms of action of the nucleic acid chaperone proteins.


id: cord-260835-ck9z5xsd
author: Kamau, Anthony Ndirangu
date: 2017-01-02
txt: ./txt/cord-260835-ck9z5xsd.txt
cache: ./cache/cord-260835-ck9z5xsd.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170216304725
doi: 10.1016/j.virusres.2016.10.004
summary:
  Results showed PEDV infection was restricted to pAPN and pAPN domain VII expressing NIH3T3 cells. Also, PEDV harvested from pAPN or domain VII expressing NIH3T3 cells was induced indirect plaques in Vero cells confirming successful entry and replication. In the current study, by constitutive expression of pAPN in non-susceptible NIH3T3 cells, we have sought to annotate the previous findings stipulating pAPN receptor function for PEDV. Susceptibility assays showed infection in pAPN domain-VII expressing cells but virus entry was abrogated in absence of seventh domain (pAPN DI-VI ) as shown in (Fig. 5A) . PEDV was also reported to interact with pAPN in porcine enterocytes (Li et al., 2009) , and is capable of infecting MDCK and ST cells expressing the pAPN receptor (Oh et al., 2003; Nam and Lee, 2010) . In our study, to determine the specific interactive point of pAPN wt with PEDV, domain mutants were expressed stably in NIH3T3 cells.

title:
  Porcine amino peptidase N domain VII has critical role in binding and entry of porcine epidemic diarrhea virus

abstract:
  Porcine epidemic diarrhea virus (PEDV) infects swine intestinal cells causing enteric disease. Research has shown that the entry into these cells is through porcine aminopeptidase N (pAPN) receptor. To gain insights into mechanisms of PEDV-pAPN interactions, the present study aimed at identifying the domain that is critical for PEDV binding. To this end, NIH3T3 cell lines constitutively expressing pAPN or pAPN mutants were generated. The mutants were; domain VII deletion mutant and domains IV–VI deletion mutant. In the latter, domain VII was linked to the transmembrane segment through domain III. Results showed PEDV infection was restricted to pAPN and pAPN domain VII expressing NIH3T3 cells. Further, reducing PEDV titre 10 fold resulted in 37.8% decrease in foci indicating positive correlation. A time course test at 12, 24, 36, 48 and 60 h showed that foci increased 6 fold in the overall time range. Also, PEDV harvested from pAPN or domain VII expressing NIH3T3 cells was induced indirect plaques in Vero cells confirming successful entry and replication. Collectively, our results demonstrate that PEDV recognizes pAPN and that the main interactive point is lodged within domain VII of the pAPN. These findings are important for therapeutic development as well as creating a platform for future studies on PEDV.


id: cord-261388-d56ci0hl
author: Tibbles, K.W
date: 1999-05-28
txt: ./txt/cord-261388-d56ci0hl.txt
cache: ./cache/cord-261388-d56ci0hl.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170299000118
doi: 10.1016/s0168-1702(99)00011-8
summary:
  Previous studies in vitro of the processing of cloned polyprotein fragments from the coronavirus infectious bronchitis virus (IBV) large open reading frame (ORF1), confirmed the activity of a predicted 3C-like proteinase (3CLP) domain and suggested that the proteinase is released autocatalytically from the polyprotein in the form of a 35 kDa protein, 3CLpro, capable of further cleavages in trans. The bacterial expression system described utilises the minimum processing unit identified in our previous studies which established that, in addition to the 3CLP domain, MP2 protein sequence between the Q/S 4 cleavage target and a point delimited by an NcoI restriction site (ntd position 10118) was that minimally required for processing. Identification of a 24-kDa polypeptide processed from the coronavirus infectious bronchitis virus 1a polyprotein by the 3C-like proteinase and determination of its cleavage sites

title:
  Activity of a purified His-tagged 3C-like proteinase from the coronavirus infectious bronchitis virus

abstract:
  Previous studies in vitro of the processing of cloned polyprotein fragments from the coronavirus infectious bronchitis virus (IBV) large open reading frame (ORF1), confirmed the activity of a predicted 3C-like proteinase (3CLP) domain and suggested that the proteinase is released autocatalytically from the polyprotein in the form of a 35 kDa protein, 3CLpro, capable of further cleavages in trans. In order to identify such cleavages within the ORF1 polyprotein mediated by 3CLpro, the proteinase was expressed in bacteria, purified and used in trans cleavage assays with polyprotein fragments lacking the 3CLP domain as targets. The proteinase was expressed as a polyprotein fragment which was able to process during expression in bacterial cells, releasing mature 3CLpro. A histidine (His(6)) tag was introduced close to the C-terminus of the proteinase to aid purification. Processing demonstrated by the tagged proteinase was indistinguishable from that of the wild-type enzyme indicating that the site chosen for the tag was permissive. From these studies we were able to demonstrate trans cleavages consistent with the use of most of the previously predicted or identified sites within the open reading frame of gene 1. This tentatively completes the processing map for the ORF1 region with respect to 3CLpro.


id: cord-262760-mf1pn587
author: Weber, Stefanie
date: 2020-09-24
txt: ./txt/cord-262760-mf1pn587.txt
cache: ./cache/cord-262760-mf1pn587.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32979477/
doi: 10.1016/j.virusres.2020.198170
summary:
  By analyzing sequence data deposited between December 2019 and end of May 2020, we have compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the US, and India to the sequence of the Wuhan isolate. More specifically, the absence of the distinct hotspot mutations in the majority of sequences from samples isolated in China, convincingly argues against the possibility of technical problems during the generation of SARS-CoV-2 nucleotide sequences. and predominate in human populations with different geographic, societal, and genetic backgrounds At the time of beginning our analyses, about 2.500 nucleotide sequences of SARS-CoV-2 had been published of which 570 were randomly selected and compared to the reference sequence of the Wuhan isolate from late 2019 (NCBI Reference Sequence: NC_045512.2). The data on the analyses of 112 isolates from the US confirmed the steady rise in mutation frequencies as SARS-CoV-2 spread to different parts of the world (Table S4 ).

title:
  Signal hotspot mutations in SARS-CoV-2 genomes evolve as the virus spreads and actively replicates in different parts of the world

abstract:
  Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China late in 2019. Nine months later (Sept. 18, 2020), the virus has infected > 30 million people world-wide and caused > 944.000 (3.15 %) fatalities in 220 countries and territories. Research on the genetics of the SARS-CoV-2 genome, its mutants and their penetrance can aid future defense strategies. By analyzing sequence data deposited between December 2019 and end of May 2020, we have compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the US, and India to the sequence of the Wuhan isolate. During world-wide spreading among human populations, at least 10 distinct hotspot mutations had been selected and found in up to > 80 % of viral genomes. Many of these mutations led to amino acid exchanges in replication-relevant viral proteins. Mutations in the SARS-CoV-2 genome would also impinge upon the secondary structure of the viral RNA molecule and its repertoire of interactions with essential cellular and viral proteins. The increasing frequency of SARS-CoV-2 mutation hotspots might select for dangerous viral pathogens. Alternatively, in a 29.900 nucleotide-genome, there might be a limit to the number of mutable and selectable sites which, when exhausted, could prove disadvantageous to viral survival. The speed, at which novel SARS-CoV-2 mutants are selected and dispersed around the world, could pose problems for the development of vaccines and therapeutics.


id: cord-263178-lvxxdvas
author: Shan, Dan
date: 2018-05-02
txt: ./txt/cord-263178-lvxxdvas.txt
cache: ./cache/cord-263178-lvxxdvas.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170217309103
doi: 10.1016/j.virusres.2018.04.013
summary:
  To study the roles of hypervariable regions (HVRs) in receptor-binding subunit S1 of the spike protein, we manipulated the genome of the IBV Beaudette strain using a reverse genetics system to construct seven recombinant strains by separately or simultaneously replacing the three HVRs of the Beaudette strain with the corresponding fragments from a QX-like nephropathogenic isolate ck/CH/LDL/091022 from China. We could not detect the replication with ck/CH/ LDL/091022 in Vero cells, so the neutralization tests were performed in 9-day-old SPF embryonated eggs to confirm whether the serotypes of the recombinant IBVs belonged to ck/CH/LDL/091022. Viral antigen was observed in Vero cells infected with the Beaudette strain and the seven recombinant IBVs (Fig. 1b) . S1 gene sequencing results confirmed that the heterogenous HVRs were stably maintained in the recombinant IBVs (Sup Fig. 1) , and no additional mutations were detected in the S protein after three passages in cells or eggs.

title:
  Effects of hypervariable regions in spike protein on pathogenicity, tropism, and serotypes of infectious bronchitis virus

abstract:
  To study the roles of hypervariable regions (HVRs) in receptor-binding subunit S1 of the spike protein, we manipulated the genome of the IBV Beaudette strain using a reverse genetics system to construct seven recombinant strains by separately or simultaneously replacing the three HVRs of the Beaudette strain with the corresponding fragments from a QX-like nephropathogenic isolate ck/CH/LDL/091022 from China. We characterized the growth properties of these recombinant IBVs in Vero cells and embryonated eggs, and their pathogenicity, tropism, and serotypes in specific pathogen-free (SPF) chickens. All seven recombinant IBVs proliferated in Vero cells, but the heterogenous HVRs could reduce their capacity for adsorption during in vitro infection. The recombinant IBVs did not significantly increase the pathogenicity compared with the Beaudette strain in SPF chickens, and they still shared the same serotype as the Beaudette strain, but the antigenic relatedness values between the recombinant strain and Beaudette strain generally decreased with the increase in the number of the HVRs exchanged. The results of this study demonstrate the functions of HVRs and they may help to develop a vaccine candidate, as well as providing insights into the prevention and control of IBV.


id: cord-263439-oquk4t96
title: Clathrin- and serine proteases-dependent uptake of porcine epidemic diarrhea virus into Vero cells
author: Park, Jung-Eun
date: 2014-10-13
txt: ./txt/cord-263439-oquk4t96.txt
cache: ./cache/cord-263439-oquk4t96.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170214003001
doi: 10.1016/j.virusres.2014.07.022
summary:
  Similar to other coronaviruses, PEDV spike protein mediates its cell entry by binding to cellular receptors and inducing membrane fusion between viral envelopes and cellular membranes. Taken together, our findings reveal that PEDV enters Vero cells via clathrin-mediated endocytosis and requires serine proteolysis during infection. Based on these observations, we concluded that an exogenous protease, like trypsin, was necessary to induce cell-cell fusion in PEDV-infected Vero cells but not essentially required for virus-cell entry. So, we hypothesized that PEDV entry into Vero cells under the trypsin-free condition most likely occurred inside endosomal compartments where cellular proteases might operate similar to trypsin, facilitating S-mediated fusion of PEDV with the endosomal membrane. The infection inhibition assay using various substrates that interfere with endocytosis or lysosomotropic agents revealed that PEDV enters Vero cells via clathrin-mediated endocytic uptake and delivery of virus to an acidic intracellular compartment.

abstract:
  Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus, is a causative agent of porcine enteric disease characterized by acute watery diarrhea and dehydration in sucking piglet. Similar to other coronaviruses, PEDV spike protein mediates its cell entry by binding to cellular receptors and inducing membrane fusion between viral envelopes and cellular membranes. However, the entry mechanism of PEDV is not studied. Here, we determined the entry mechanism of PEDV into Vero cells. Our data confirmed that PEDV entry followed clathrin-mediated endocytosis independence of caveolae-coated pit assembly. The internalized PEDV was co-localized with the clathrin-mediated endocytic marker, but not with the caveolae-mediated endocytic marker. In addition, cells treated with lysosomotropic agents and serine protease inhibitors were resistant to PEDV. Our data revealed that PEDV entry followed clathrin-mediated endocytosis and was dependent on a low pH and serine proteolysis for successful entry into cells.


id: cord-266025-bkm486jd
title: Genomic characterization of seven distinct bat coronaviruses in Kenya()
author: Tao, Ying
date: 2012-04-26
txt: ./txt/cord-266025-bkm486jd.txt
cache: ./cache/cord-266025-bkm486jd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22561208/
doi: 10.1016/j.virusres.2012.04.007
summary:
  Based on available data, bats appear to harbor a great diversity of CoVs. The frequency and diversity of CoV detection in bats, now in multiple continents, suggest that bats are likely a source for CoV introduction into other species globally and possibly play an important role in the ecology and evolution of CoVs. Recently we reported the identification of 41 divergent CoVs in bats from Kenya, based on limited ORF1b sequences (Tong et al., 2009) . The aa distances in the 816 bp fragment of the RdRp gene from the Kenya bat CoVs described in this study were compared to the aa sequences from their close reference viruses (Table S2) . In conclusion, sequence data for the structural and nonstructural ORFs in the 3 -end of the genome of seven Kenya bat CoVs confirmed the high diversity and their phylogenetical placement into Alphacoronavirus and Betacoronavirus genera. Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences

abstract:
  To better understand the genetic diversity and genomic features of 41 coronaviruses (CoVs) identified from Kenya bats in 2006, seven CoVs as representatives of seven different phylogenetic groups identified from partial polymerase gene sequences, were subjected to extensive genomic sequencing. As a result, 15–16 kb nucleotide sequences encoding complete RNA dependent RNA polymerase, spike, envelope, membrane, and nucleocapsid proteins plus other open reading frames (ORFs) were generated. Sequences analysis confirmed that the CoVs from Kenya bats are divergent members of Alphacoronavirus and Betacoronavirus genera. Furthermore, the CoVs BtKY22, BtKY41, and BtKY43 in Alphacoronavirus genus and BtKY24 in Betacoronavirus genus are likely representatives of 4 novel CoV species. BtKY27 and BtKY33 are members of the established bat CoV species in Alphacoronavirus genus and BtKY06 is a member of the established bat CoV species in Betacoronavirus genus. The genome organization of these seven CoVs is similar to other known CoVs from the same groups except for differences in the number of putative ORFs following the N gene. The present results confirm a significant diversity of CoVs circulating in Kenya bats. These Kenya bat CoVs are phylogenetically distant from any previously described human and animal CoVs. However, because of the examples of host switching among CoVs after relatively minor sequence changes in S1 domain of spike protein, a further surveillance in animal reservoirs and understanding the interface between host susceptibility is critical for predicting and preventing the potential threat of bat CoVs to public health.


id: cord-266453-v1hbust8
author: Sztuba-Solińska, Joanna
date: 2012-10-16
txt: ./txt/cord-266453-v1hbust8.txt
cache: ./cache/cord-266453-v1hbust8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23079110/
doi: 10.1016/j.virusres.2012.10.001
summary:
  We have previously described the efficient homologous recombination system between 5′ subgenomic RNA3a (sgRNA3a) and genomic RNA3 of Brome mosaic virus (BMV) in barley protoplasts (Sztuba-Solińska et al., 2011a). A structured region near the 3 sgRNA3a polyA tail, referred to as the intergenic Bbox motif, participates in the assembly of the BMV replicase complex on RNA3 via interactions with protein 1a (Baumstrak and Ahlquist, 2001) , and it binds CP molecules via a specific peptide domains, as mapped by Yi et al. In a separate experiment, the Bbox-RNA3 was co-transfected with SG construct to determine whether the presence of the wt Bbox motif in sgRNA3a could rescue the previously reported high recombination frequency for unmutated RNAs. Indeed, among 100 cDNA clones, there were 42 recombinants (Fig. 2B) , of which the majority carried all three marker restriction sites (74%, 32 clones), while few had either single (BamHI -four clones) or double (BamHI/HindIII -three clones, BamHI/PstI -one clone, HindIII/PstI -two clones) restriction sites.

title:
  Mutations in the coat protein-binding cis-acting RNA motifs debilitate RNA recombination of Brome mosaic virus

abstract:
  We have previously described the efficient homologous recombination system between 5′ subgenomic RNA3a (sgRNA3a) and genomic RNA3 of Brome mosaic virus (BMV) in barley protoplasts (Sztuba-Solińska et al., 2011a). Here, we demonstrated that sequence alterations in the coat protein (CP)-binding cis-acting RNA motifs, the Bbox region (in the intercistronic RNA3 sequence) and the RNA3 packaging element (PE, in the movement protein ORF), reduced crossover frequencies in protoplasts. Additionally, the modification of Bbox-like element in the 5′ UTR region strongly debilitated crossovers. Along the lines of these observations, RNA3 mutants not expressing CP or expressing mutated CPs also reduced recombination. A series of reciprocal transfections demonstrated a functional crosstalk between the Bbox and PE elements. Altogether, our data imply the role of CP in sgRNA3a-directed recombination by either facilitating the interaction of the RNA substrates and/or by creating roadblocks for the viral replicase.


id: cord-267228-g2tf1jz6
author: Huang, Ke-Yan
date: 2018-03-02
txt: ./txt/cord-267228-g2tf1jz6.txt
cache: ./cache/cord-267228-g2tf1jz6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29288673/
doi: 10.1016/j.virusres.2017.12.011
summary:
  Mice were immunized by lavage administration of the recombinant NC8-pSIP409-pgsA''-S-DCpep, which was observed to induce DC activation and high production of sIgA and IgG antibodies in experimental animals, while also eliciting production of significantly more IgA(+)B220(+) B cells. Compared with the saline group, the expression level of CD11c + CD40 + of DCs surface molecules in the LP cells of the small intestine was significantly increased in the NC8-pSIP409-pgsA''-S-DCpep group (P < 0.01) and NC8-pSIP409-pgsA''-S-Ctrlpep group (P < 0.05) experimental groups (Fig. 2B) . Unexpectedly, the level of IFN-γ in the supernatant of MLN cells cultured with the strains expressing S-DCpep was significantly higher in the group of mice orally immunized with recombinant NC8-pSIP409-pgsA''-S-Dcpep compare to the group of mice orally administered with saline (P < 0.01), NC8-pSIP409-pgsA''-S-Ctrlpep and NC8-pSIP409-pgsA'' groups (P < 0.05) (Fig. 6B ).

title:
  Construction and immunogenicity analysis of Lactobacillus plantarum expressing a porcine epidemic diarrhea virus S gene fused to a DC-targeting peptide

abstract:
  Porcine epidemic diarrhea virus (PEDV) is one of the most important causative pathogens of swine diarrhea, which is widely prevalent throughout the world and is responsible for significant economic losses in the commercial pig industry, both domestic and abroad. The spike (S) protein in the PEDV capsid structure can carry the major B lymphocyte epitope, which induces production of neutralizing antibodies and provides immunoprotective effects. Moreover, the conserved region encoded by the S gene can be considered a target for establishing a new diagnostic method and is a new candidate for vaccine design. In this study, use of anchorin pgsA' allowed the fusion protein of S-DCpep to express on the surface of recombinant Lactobacillus plantarum (NC8-pSIP409-pgsA'-S-DCpep) NC8 strain. Mice were immunized by lavage administration of the recombinant NC8-pSIP409-pgsA'-S-DCpep, which was observed to induce DC activation and high production of sIgA and IgG antibodies in experimental animals, while also eliciting production of significantly more IgA(+)B220(+) B cells. More importantly, secretion of cytokines IFN-γ, IL-4 and IL-17 in mice that were vaccinated with NC8-pSIP409-pgsA'-S-DCpep was remarkably increased. The results of our study suggest that NC8-pSIP409-pgsA'-S-DCpep potently triggers cellular and humoral immune responses. The obtained experimental results can provide a theoretical basis that lays the foundation for production of a novel oral vaccine against PED.


id: cord-267362-l4288mxw
author: Shi, Xibao
date: 2010-08-06
txt: ./txt/cord-267362-l4288mxw.txt
cache: ./cache/cord-267362-l4288mxw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20692306/
doi: 10.1016/j.virusres.2010.07.028
summary:
  title: Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing system and had mechanisms to inhibit this action in MARC-145 cells The obtained results showed that PRRSV nsp1 could inhibit Poly(I:C)-induced IFN-β promoter activity in MARC-145 cells by down-regulating the protein level of IRF-3 and inhibiting the phosphorylation of IRF-3. These PAMPs recruit different adaptor proteins, for example, TLRs recruits the adaptor molecule myeloid differentiation primary-response gene 88(MyD88) and Toll/IL-1 receptor domain-containing adaptor inducing IFN(TRIF) while RIG-I recruits virus-induced signaling adapter (VISA), to make TANK-binding kinase 1 (TBK1) or IB kinase-(IKK-) phosphorylate IRF-3 and finally to induce IFN-␤ transcription (Bowie and Unterholzner, 2008) . So, the purpose of the present experiments is to analyze the patterns of IFN-␤ promoter activity in MARC-145 cells during infection with PRRSV and to analyze whether PRRSV nsp1 and N protein could inhibit IFN-␤ production.

title:
  Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing system and had mechanisms to inhibit this action in MARC-145 cells

abstract:
  Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important disease in swine-producing area, and interferon beta (IFN-β) is the first responder against the animal virus infection. However, whether PRRSV could induce the production of IFN-β is controversial. In this paper, we first time found that PRRSV could phosphorylate IFN-regulatory factor 3 (IRF-3) and weakly activate the IFN-β promoter in MARC-145 cells in early infection, but the activations of IRF-3 and IFN-β promoter were rapidly inhibited in the following infection. Furthermore, which components or products of the invading PRRSV cause PRRSV to inhibit IFN-β promoter activity attracted our attentions. The obtained results showed that PRRSV nsp1 could inhibit Poly(I:C)-induced IFN-β promoter activity in MARC-145 cells by down-regulating the protein level of IRF-3 and inhibiting the phosphorylation of IRF-3. In conclusion, our results suggested that PRRSV could be sensed by professional IFN-β-producing system and had mechanisms to inhibit this action in MARC-145 cells.


id: cord-267363-5qri915n
title: Meta-transcriptomics and the evolutionary biology of RNA viruses
author: Shi, Mang
date: 2018-01-02
txt: ./txt/cord-267363-5qri915n.txt
cache: ./cache/cord-267363-5qri915n.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170217305452
doi: 10.1016/j.virusres.2017.10.016
summary:
  As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. As well as greatly expanding our knowledge of virus diversity, including the ''dark matter'' of highly divergent viruses that often elude characterization, these new data will enable us to determine the fundamental evolutionary and ecological processes that shape the virosphere, and better understand the virus-host interactions that lead to disease emergence.

abstract:
  Metagenomics is transforming the study of virus evolution, allowing the full assemblage of virus genomes within a host sample to be determined rapidly and cheaply. The genomic analysis of complete transcriptomes, so-called meta-transcriptomics, is providing a particularly rich source of data on the global diversity of RNA viruses and their evolutionary history. Herein we review some of the insights that meta-transcriptomics has provided on the fundamental patterns and processes of virus evolution, with a focus on the recent discovery of a multitude of novel invertebrate viruses. In particular, meta-transcriptomics shows that the RNA virus world is more fluid than previously realized, with relatively frequent changes in genome length and structure. As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. Given that most viruses in the future will likely be characterized using metagenomics approaches, and that we have evidently only sampled a tiny fraction of the total virosphere, we suggest that proposals for virus classification pay careful attention to the wonders unearthed in this new age of virus discovery.


id: cord-268010-1m5h3krw
author: Jung, Kwonil
date: 2016-12-02
txt: ./txt/cord-268010-1m5h3krw.txt
cache: ./cache/cord-268010-1m5h3krw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27086031/
doi: 10.1016/j.virusres.2016.04.009
summary:
  However, a recent study reported evidence of antigenic cross-reactivity between PDCoV Michigan/8977/2014 strain and PEDV, possibly sharing at least one conserved or similar epitope on their N proteins, as determined by enzyme-linked immunosorbent assay (ELISA) and western blot using monoclonal PEDV and PDCoV N-specific antibodies, whereas no cross-reactivity was detected when virus neutralization, indirect immunofluorescence, and immunostaining assays were conducted on either virus-infected cells or intestinal tissues using pig hyperimmune antisera to PEDV or PDCoV (Ma et al., 2016) . Another study using conventional 5-day-old pigs and a cell culture-adapted PDCoV USA/IL/2014 strain (P11) reported the onset of diarrhea at PID 5 in 5 of 5 pigs orally inoculated with 3 × 10 4 TCID 50 /pig of the virus, which was 1 day later or coincided with the detection of viral RNA in feces at PID 4 (3/5 pigs tested) or 5 (2/5 pigs tested) (Chen et al., 2015b) .

title:
  Porcine deltacoronavirus infection: Etiology, cell culture for virus isolation and propagation, molecular epidemiology and pathogenesis

abstract:
  Porcine deltacoronavirus (PDCoV) (family Coronaviridae, genus Deltacoronavirus) is a novel swine enteropathogenic coronavirus that causes acute diarrhea/vomiting, dehydration and mortality in seronegative neonatal piglets. PDCoV diarrhea was first reported in the US in early 2014, concurrently with co-circulation of porcine epidemic diarrhea virus (PEDV) (family Coronaviridae, genus Alphacoronavirus). The origin of PDCoV in pigs and also its sudden emergence or route of introduction into the US still remains unclear. In the US, since 2013–2014, the newly emerged PDCoV and PEDV have spread nationwide, causing a high number of pig deaths and significant economic impacts. The current US PDCoV strains are enteropathogenic and infect villous epithelial cells of the entire small and large intestines although the jejunum and ileum are the primary sites of infection. Similar to PEDV infections, PDCoV infections also cause acute, severe atrophic enteritis accompanied by transient viremia (viral RNA) that leads to severe diarrhea and/or vomiting, followed by dehydration as the potential cause of death in nursing piglets. At present, differential diagnosis of PDCoV, PEDV, and transmissible gastroenteritis virus (TGEV) is essential to control viral diarrheas in US swine. Cell culture-adapted US PDCoV (TC-PDCoV) strains have been isolated and propagated by us and in several other laboratories. TC-PDCoV strains will be useful to develop serologic assays and to evaluate if serial cell-culture passage attenuates TC-PDCoV as a potential vaccine candidate strain. A comprehensive understanding of the pathogenesis and epidemiology of epidemic PDCoV strains is currently needed to prevent and control the disease in affected regions and to develop an effective vaccine. This review focuses on the etiology, cell culture isolation and propagation, molecular epidemiology, disease mechanisms and pathogenesis of PDCoV infection.


id: cord-268337-o6lo55o8
title: Translational control by viral proteinases
author: Lloyd, Richard E.
date: 2005-11-21
txt: ./txt/cord-268337-o6lo55o8.txt
cache: ./cache/cord-268337-o6lo55o8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16303201/
doi: 10.1016/j.virusres.2005.10.016
summary:
  Human immunodeficiency virus-1 (HIV-1) infection of cells resulted in partial cleavages of eIF4GI that was mapped to three sites in two regions on either side of the eIF3-binding domain ( Fig. 1) (Ohlmann et al., 2002; Ventoso et al., 2001) . Translation assays based on luciferase reporter constructs in cells indicated that expression of HIV protease (HIV PR) primarily inhibited translation of capped mRNAs. Interestingly, comparison of translation function of eIF4GI C-terminal cleavage products produced by L pro and HIV PR revealed that the slightly shorter HIV PR-derived fragment was defective in supporting translation of the PV-IRES but not the EMCV IRES. Demonstration in vitro that eucaryotic initiation factor 3 is active but a cap-binding protein complex is inactive in poliovirus-infected HeLa cells Eukaryotic initiation factor 4GII (eIF4GII), but not eIF4GI, cleavage correlates with inhibition of host cell protein synthesis after human rhinovirus infection Cleavage of eukaryotic initiation factor eIF4G and inhibition of host-cell protein synthesis during feline calicivirus infection

abstract:
  Most RNA viruses have evolved strategies to regulate cellular translation in order to promote preferential expression of the viral genome. Positive strand RNA viruses express large portions, or all of their proteome via translation of large polyproteins that are processed by embedded viral proteinases or host proteinases. Several of these viral proteinases are known to interact with host proteins, particularly with the host translation machinery, and thus, encompass the dual functions of processing of viral polyproteins and exerting translation control. Picornaviruses are perhaps the best characterized in regards to interaction of their proteinases with the host translation machinery and will be emphasized here. However, new findings have shown that similar paradigms exist in other viral systems which will be discussed.


id: cord-268930-y1cm58r6
title: Expression, purification, and in vitro activity of an arterivirus main proteinase
author: van Aken, Danny
date: 2006-03-09
txt: ./txt/cord-268930-y1cm58r6.txt
cache: ./cache/cord-268930-y1cm58r6.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170206000608
doi: 10.1016/j.virusres.2006.01.025
summary:
  To allow the biochemical and structural characterization of the chymotrypsin-like "main proteinase" (non-structural protein 4; nsp4) of the arterivirus prototype Equine Arteritis Virus (EAV), we developed protocols for the large-scale production of recombinant nsp4 in Escherichia coli. In a synthetic peptide-based activity assay, the potential of the recombinant proteinase to cleave peptides mimicking the P9–P7′ residues of six nsp4 cleavage sites was investigated. To test whether active recombinant proteinases had been isolated, the proteolytic activity of purified MBP-nsp4 and nsp4His was tested in cleavage assays using in vitro synthesized substrates as described in Section 2. Although it was reported that the addition of six His residues strongly inhibited the enzymatic activity of the human coronavirus 229E 3CL pro proteinase (Ziebuhr et al., 1997) , in both our assays the catalytic activity of nsp4His was very comparable to that of partially purified uncleaved or cleaved MBP-nsp4.

abstract:
  To allow the biochemical and structural characterization of the chymotrypsin-like “main proteinase” (non-structural protein 4; nsp4) of the arterivirus prototype Equine Arteritis Virus (EAV), we developed protocols for the large-scale production of recombinant nsp4 in Escherichia coli. The nsp4 proteinase was expressed either fused to maltose binding protein or carrying a C-terminal hexahistidine tag. Following purification, the nsp4 moiety of MBP-nsp4 was successfully used for structural studies [Barrette-Ng, I.H., Ng, K.K.S., Mark, B.L., van Aken, D., Cherney, M.M., Garen, C, Kolodenko, Y., Gorbalenya, A.E., Snijder, E.J., James, M.N.G, 2002. Structure of arterivirus nsp4—the smallest chymotrypsin-like proteinase with an alpha/beta C-terminal extension and alternate conformations of the oxyanion hole. J. Biol. Chem. 277, 39960–39966]. Furthermore, both forms of the EAV proteinase were shown to be proteolytically active in two different trans-cleavage assays. Recombinant nsp4 cleaved the cognate nsp6/7- and nsp7/8 site in in vitro synthesized substrates. In a synthetic peptide-based activity assay, the potential of the recombinant proteinase to cleave peptides mimicking the P9–P7′ residues of six nsp4 cleavage sites was investigated. The peptide representing the EAV nsp7/8 junction was used to optimize the reaction conditions (pH 7.5, 25 mM NaCl, 30% glycerol at 30 °C), which resulted in a maximum turnover of 15% of this substrate in 4 h, using a substrate to enzyme molar ratio of 24:1. The assays described in this study can be used for a more extensive biochemical characterization of the EAV main proteinase, including studies aiming to identify inhibitors of proteolytic activity.


id: cord-270064-hidirfkv
title: A COMPREHENSIVE ANALYSIS OF GENOME COMPOSITION AND CODON USAGE PATTERNS OF EMERGING CORONAVIRUSES
author: Tort, Fernando L.
date: 2020-04-12
txt: ./txt/cord-270064-hidirfkv.txt
cache: ./cache/cord-270064-hidirfkv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32294518/
doi: 10.1016/j.virusres.2020.197976
summary:
  In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. In order to gain insight into the emergence, evolution, adaptation and spread of the SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. To gain insight into the biology and evolution of emerging SARS-CoV-2, a comprehensive analysis of genome composition, codon and amino acid usage of βCoV strains isolated in China from humans, bats, civets and ferret hosts was performed, including SARS-CoV-2 strains recently isolated from current outbreak. The results of these studies revealed that SARS-CoV-2 strains enrolled in these analyses have a distinct genome composition in relation to other βCoV strains isolated from human (SARS-CoV), bats, civets and ferrets (see Fig. 1 ).

abstract:
  An outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS-CoV-2 has been declared a public health emergency of international concern by the World Health Organization. In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. A biased nucleotide composition was found for SARS-CoV-2 genome. This bias in genomic composition is reflected in its codon and amino acid usage patterns. The overall codon usage in SARS-CoV-2 is similar among themselves and slightly biased. Most of the highly frequent codons are A- and U-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. Significant differences in relative synonymous codon usage frequencies among SARS-CoV-2 and human cells were found. These differences are due to codon usage preferences.


id: cord-271568-qgpi2kcs
author: Jackwood, M.W.
date: 2010-01-21
txt: ./txt/cord-271568-qgpi2kcs.txt
cache: ./cache/cord-271568-qgpi2kcs.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2010.01.006
doi: 10.1016/j.virusres.2010.01.006
summary:
  Genomic diversity and the Abbreviations: CPE, cytopathic effects; EID50, 50% embryo infectious dose; ELISA, enzyme linked immunosorbent assay; HMA, hexamethylene amiloride; IBV, infectious bronchitis virus; MHV, mouse hepatitis virus; PBS, phosphate buffered saline; RFLP, restriction fragment length polymorphism; RT-PCR, reverse transcriptasepolymerase chain reaction; SARS-CoV, Severe Acute Respiratory Syndrome virus; SPF, specific pathogen free; TCID50, 50% tissue culture infectious dose. Clinical signs were observed in all of the Mass41 virus challenged groups of birds regardless of treatment but in the intranasal and spray treated groups, fewer birds had signs and the signs were milder, as reflected by lower average scores (Table 1) . Virus was detected in 1 of 5 vaccinated birds in the treated group at 7 days post-vaccination Table 3 Experiment 4: clinical signs a in broiler chickens challenged with IBV at various times after treatment with QR448(a) at 1 day of age.

title:
  Avian coronavirus infectious bronchitis virus susceptibility to botanical oleoresins and essential oils in vitro and in vivo

abstract:
  Anti-coronaviral activity of a mixture of oleoresins and essential oils from botanicals, designated QR448(a), was examined in vitro and in vivo. Treatment of avian infectious bronchitis virus (IBV) with QR448(a) reduced the virus titer as measured in two laboratory host systems, Vero E6 cells and embryonating eggs. The effect of QR448(a) on IBV in chickens was also investigated. Administering QR448(a) to chickens at a 1:20 dilution by spray, 2 h before challenge with IBV was determined to be the most effective treatment. Treatment decreased the severity of clinical signs and lesions in the birds, and lowered the amount of viral RNA in the trachea. Treatment with QR448(a) protected chickens for up to 4 days post-treatment from clinical signs of disease (but not from infection) and decreased transmission of IBV over a 14-day period. Anti-IBV activity of QR448(a) was greater prior to virus attachment and entry indicating that the effect is virucidal. In addition, QR448(a) had activity against both Massachusetts and Arkansas type IB viruses, indicating that it can be expected to be effective against IBV regardless of serotype. To our knowledge, this is the first report on the in vivo use of a virucidal mixture of compounds effective against the coronavirus IBV.


id: cord-272383-pzivb0ro
author: Reddy, P.Seshidhar
date: 2000-11-08
txt: ./txt/cord-272383-pzivb0ro.txt
cache: ./cache/cord-272383-pzivb0ro.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170200002094
doi: 10.1016/s0168-1702(00)00209-4
summary:
  In an effort to optimize the expression, we have constructed several BAV-3 recombinants carrying the hemagglutinin esterase (HE) gene of bovine coronavirus (BCV) in the E3 region with or without exogenous transcription control elements. During infection of bovine cell lines, such recombinant BAVs produced large amounts of glycoprotein gD (a DNA virus gene), which has been shown to undergo proper post-translational modifications . This new transfer vector has two unique restriction enzyme sites (SrfI and SalI) for cloning of foreign genes and an overlap of 1992 bp on the left side and 3866 bp on the right side of the E3 region for efficient homologous recombination with plasmid pFBAV-302 , which dramatically increased the frequency of recombination in BJ 5183 cells. Our initial attempts to insert the BCV HE gene in the E3 region of plasmid pFBAV302 (E3 deleted full length BAV-3 genomic clone; Zakhartchouk et al., 1998) by homologous recombination in E.

title:
  Optimization of bovine coronavirus hemagglutinin-estrase glycoprotein expression in E3 deleted bovine adenovirus-3

abstract:
  Adenoviral vectors expressing foreign genes have many desirable properties in applications such as vaccination. Recently, we have generated replication-competent (E3 deleted) bovine adenovirus-3 (BAV-3) recombinants expressing significant amounts of glycoprotein D (gD) of bovine herpesvirus-1 (a DNA virus). However, attempts to express the RNA virus genes using the same strategy were not successful. In an effort to optimize the expression, we have constructed several BAV-3 recombinants carrying the hemagglutinin esterase (HE) gene of bovine coronavirus (BCV) in the E3 region with or without exogenous transcription control elements. The expression studies suggest that the introduction of a 137 bp chimeric intron upstream of the HE cDNA is able to increase the level of HE gene expression. The introduction of a SV40 early promoter or human cytomegalovirus (HCMV) immediate early (IE) promoter into the expression cassette changed the kinetics of the HE expression. However, the recombinant BAV-3 containing HE under the HCMV IE promoter replicated less efficiently than the wild-type BAV-3. These studies should prove useful in expression of other RNA viral genes in the E3 region of BAV-3 expression system.


id: cord-272408-8flsy5o1
author: Chen, Rui
date: 2020-01-15
txt: ./txt/cord-272408-8flsy5o1.txt
cache: ./cache/cord-272408-8flsy5o1.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170219302850
doi: 10.1016/j.virusres.2019.197834
summary:
  The neutralizing activity of the rabbit and mouse anti -NTD, -CTD, and -S2 polyclonal antisera was assessed 4 weeks after the initial inoculation by a FFN assay, as previously described (Okda et al., 2015) . Sera from rabbits inoculated with NTD, CTD, and S2 were tested for neutralizing antibodies against PDCoV by ELISA, virus neutralization (VN), and fluorescent focus neutralization (FFN) assays. These results demonstrate that the NTD, CTD, and S2 proteins induced potent anti-PDCoV neutralizing antibody responses in the immunized animals. We found that three regions in PDCOV S protein, including NTD (aa 50-286), CTD (aa 278-616), and S2 (aa 601-1087), can induce neutralizing antibody responses, and the specific polyclonal mouse and rabbit sera efficiently inhibit PDCoV entry and infection in ST cells. Cell attachment domains of the porcine epidemic diarrhea virus spike protein are key targets of neutralizing antibodies

title:
  Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus

abstract:
  Porcine deltacoronavirus (PDCoV), is an emerging enteropathogenic coronavirus in pigs, that poses a novel threat to swine husbandry worldwide. Crucial to halting PDCoV transmission and infection is the development of effective therapies and vaccines. The spike (S) protein of coronavirus is the major target of host neutralizing antibodies, however the immunodominant neutralizing region in the S protein of PDCoV has not been defined. Here, three truncations of the PDCoV S protein were generated, the N-terminal domain of the S1 subunit (NTD, amino acids (aa) 50–286), the C-terminal domain of the S1 subunit (CTD, aa 278–616), and S2 subunit (aa 601–1087). The proteins were expressed using an E. coli expression system. Polyclonal antisera against the three recombinant proteins were produced in rabbits and mice. All three antisera were able to inhibit PDCoV infection in vitro, as determined by virus neutralization assay, fluorescent focus neutralization assay, and plaque-reduction neutralization. The CTD-specific antisera had the most potent PDCoV-neutralizing effect, indicating that the CTD region may contain the major neutralizing epitope(s) in the PDCoV S protein. Based on these findings, CTD may be a promising target for development of an effective vaccine against PDCoV infection in pigs.


id: cord-272458-72dybi7t
title: Activation of human monocytes after infection by human coronavirus 229E
author: Desforges, Marc
date: 2007-07-31
txt: ./txt/cord-272458-72dybi7t.txt
cache: ./cache/cord-272458-72dybi7t.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170207002304
doi: 10.1016/j.virusres.2007.06.016
summary:
  Moreover, like primary monocytes and macrophages, the THP-1 cells were highly susceptible to HCoV-229E-induced cell death, regardless of the state of differentiation, as mitochondrial metabolic activity dropped significantly at 72 hpi ( Fig. 1C) , suggesting that the decrease in infectious titers may in part be due to a lower number of viable cells. Also, similarly to primary monocytes and macrophages, the PMA-differentiated THP-1 cells restricted HCoV-OC43 replication, with no detection of production of infectious virus (Fig. 1B ) or viral antigens (data not shown). When HCoV-229E infection of human primary monocytes/macrophages was performed at a MOI of 1, infectious virus was under the detection limit at 3 dpi but viral antigens were still easily detected within the infected cells until at least 5 dpi (data not shown). When HCoV-229E infection of both primary monocytes and THP-1 cells was performed at a MOI of 0.1, the kinetics of infection was similar, as shown by infectious virus production ( Fig. 2A) and detection of viral antigens (Fig. 3A) .

abstract:
  Human coronaviruses (HCoV) are recognized respiratory pathogens that may be involved in other pathologies such as central nervous system (CNS) diseases. To investigate whether leukocytes could participate in respiratory pathologies and serve as vector for viral spread towards other tissues, the susceptibility of human leukocytic cell lines and peripheral blood mononuclear cells (PBMC) to HCoV-229E and HCoV-OC43 infection was investigated. Human primary monocytes/macrophages were susceptible to HCoV-229E infection, but strongly restricted HCoV-OC43 replication. Moreover, productive HCoV-229E infection of primary monocytes and of the THP-1 monocytic cell line led to their activation, as indicated by the production of pro-inflammatory mediators, including TNF-α, CCL5, CXCL10 and CXCL11 and MMP-9. Moreover, an in vitro chemotaxis assay showed that motility towards chemokines of THP-1 cells and primary monocytes was increased following an acute or persistent HCoV-229E infection. Taken together, these results suggest that infected monocytes could serve as a reservoir for HCoV-229E, become activated, participate in the exacerbation of pulmonary pathologies, as well as serve as potential vectors for viral dissemination to host tissues, where it could be associated with other pathologies.


id: cord-272729-nbgdmavr
title: Ribavirin efficiently suppresses porcine nidovirus replication
author: Kim, Youngnam
date: 2012-10-27
txt: ./txt/cord-272729-nbgdmavr.txt
cache: ./cache/cord-272729-nbgdmavr.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170212004078
doi: 10.1016/j.virusres.2012.10.018
summary:
  Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further experiments revealed that suppression of ribavirin affects post-entry steps of the replication cycle of PRRSV and PEDV, including viral genomic and sg RNA synthesis, viral protein expression, and virus production. Several mechanisms of action for the antiviral activity of ribavirin have been suggested, including a reduction in cellular GTP pools via inosine monophosphate dehydrogenase (IMPDH) inhibition and increased mutation frequency on the virus genome leading to error catastrophe (Graci and Cameron, 2006) . Treatment of cells with ribavirin resulted in significant attenuation of postentry steps during the replication of porcine nidovirus, as determined by lower progeny production, diminished viral protein expression, and decreased synthesis of genomic RNA and sg mRNA.

abstract:
  Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that represent emerging viral pathogens causing heavy economic impacts on the swine industry. Although ribavirin is a well-known antiviral drug against a broad range of both DNA and RNA viruses in vitro, its inhibitory effect and mechanism of action on porcine nidovirus replication remains to be elucidated. Therefore, the present study was conducted to determine whether ribavirin suppresses porcine nidovirus infection. Our results demonstrated that ribavirin treatment dose-dependently inhibited the replication of both nidoviruses. The antiviral activity of ribavirin on porcine nidovirus replication was found to be primarily exerted at early times post-infection. Treatment with ribavirin resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production in a dose-dependent manner. Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further sequencing analysis showed that the mutation frequency in ribavirin-treated cells was similar to that in untreated cells, indicating that ribavirin did not induce error-prone replication. Taken together, our data indicate that ribavirin might not only be a good therapeutic agent against porcine nidovirus, but also a potential candidate to be evaluated against other human and animal coronaviruses.


id: cord-275016-ij5yaqkx
title: Characterization of the norovirus 3C-like protease
author: Someya, Yuichi
date: 2005-03-08
txt: ./txt/cord-275016-ij5yaqkx.txt
cache: ./cache/cord-275016-ij5yaqkx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15845259/
doi: 10.1016/j.virusres.2005.02.002
summary:
  The recombinant 3C-like protease of Chiba virus, a Norovirus, expressed in Escherichia coli cells was purified and characterized as to effects of pH, temperature, salt contents, and SH reagents on its proteolytic activity. The DNA fragment encoding all residues (Ala1 to Glu181) of the Chiba virus 3C-like protease was amplified by PCR, in that NdeI and Aor51HI restriction sites were introduced at the 5 and 3 ends, respectively. In order to observe proteolysis at the cleavage site between the 3C and 3D, we at first used the His-3CD-C139A mutant protein expressed from pT7His3CD-C139A as a substrate, which was the N-terminal His-tagged 3CD fragment containing the Ala mutation of active-site Cys139 of the 3C-like protease (Fig. 1B) . They used bacterially expressed 3C-like protease with its C-terminus His-tagged as an enzyme and the entire ORF1 protein or 3CD fragment containing the active-site Cys mutation as a substrate which was expressed in the in vitro transcription/translation reaction.

abstract:
  The recombinant 3C-like protease of Chiba virus, a Norovirus, expressed in Escherichia coli cells was purified and characterized as to effects of pH, temperature, salt contents, and SH reagents on its proteolytic activity. The optimal pH and temperature of the 3C-like protease for the proteolytic activity were 8.6 and 37 °C, respectively. Increased concentration (∼100 mM) of monovalent cations such as Na(+) and K(+) was inhibitory to the activity. Hg(2+) and Zn(2+) remarkably inhibited the protease activity, while Mg(2+) and Ca(2+) had no virtual effect. Several sulfhydryl reagents such as p-chloromercuribenzoic acid, methyl methanethiosulfonate, N-ethylmaleimide and N-phenylmaleimide also blocked the activity, confirming the previous result that cysteine residue(s) were responsible for the proteolysis.


id: cord-275182-cmjfqkjz
title: Vectored vaccines to protect against PRRSV
author: Cruz, Jazmina L.G.
date: 2010-06-25
url: https://api.elsevier.com/content/article/pii/S0168170210002017
doi: 10.1016/j.virusres.2010.06.017
abstract:
  PRRSV is the causative agent of the most important infectious disease affecting swine herds worldwide, producing great economic losses. Commercially available vaccines are only partially effective in protection against PRRSV. Moreover, modified live vaccines may allow virus shedding, and could revert generating virulent phenotypes. Therefore, new efficient vaccines are required. Vaccines based on recombinant virus genomes (virus vectored vaccines) against PRRSV could represent a safe alternative for the generation of modified live vaccines. In this paper, current vectored vaccines to protect against PRRSV are revised, including those based on pseudorabies virus, poxvirus, adenovirus, and virus replicons. Special attention has been provided to the use of transmissible gastroenteritis virus (TGEV) as vector for the expression of PRRSV antigens. This vector has the capability of expressing high levels of heterologous genes, is a potent interferon-α inducer, and presents antigens in mucosal surfaces, eliciting both secretory and systemic immunity. A TGEV derived vector (rTGEV) was generated, expressing PRRSV wild type or modified GP5 and M proteins, described as the main inducers of neutralizing antibodies and cellular immune response, respectively. Protection experiments showed that vaccinated animals developed a faster and stronger humoral immune response than the non-vaccinated ones. Partial protection in challenged animals was observed, as vaccinated pigs showed decreased lung damage when compared with the non-vaccinated ones. Nevertheless, the level of neutralizing antibodies was low, what may explain the limited protection observed. Several strategies are proposed to improve current rTGEV vectors expressing PRRSV antigens.


id: cord-275413-e2rhioty
title: The interaction between PRRSV and the late gestation pig fetus
author: Rowland, Raymond R.R.
date: 2010-09-09
txt: ./txt/cord-275413-e2rhioty.txt
cache: ./cache/cord-275413-e2rhioty.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20832434/
doi: 10.1016/j.virusres.2010.09.001
summary:
  The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no.

abstract:
  Porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta during late gestation and productively infects the fetus. Virus replication and cytokine responses were measured in tissues of fetuses recovered at 109–112 days of gestation, just prior to parturition. At the time of recovery, gross anatomical abnormalities were evident in both infected and non-infected fetuses from the infected dams. Virus isolation and immunohistochemistry identified the thymus as the primary site of virus replication. Steady state RT-PCR amplification of inflammatory, Th1 and Th2 cytokines, showed elevated IFN-γ and TNF-α mRNAs in tissues from infected fetuses, which corresponded to elevated cytokine proteins in serum but not amniotic fluid. Further evidence for induction of immunity was found in the hyperplastic response of lymph nodes, which included the development of germinal centers occupied CDw75+ B cells. Collectively, these data support the notion that the immunocompetent fetus is capable of initiating an antiviral response, which is compartmentalized within the infected fetus. Furthermore, fetal pathology may not be a direct result of virus replication in the fetus.


id: cord-276198-psjua913
title: New insights on the role of paired membrane structures in coronavirus replication
author: V’kovski, Philip
date: 2015-04-16
url: https://api.elsevier.com/content/article/pii/S0168170214005358
doi: 10.1016/j.virusres.2014.12.021
abstract:
  The replication of coronaviruses, as in other positive-strand RNA viruses, is closely tied to the formation of membrane-bound replicative organelles inside infected cells. The proteins responsible for rearranging cellular membranes to form the organelles are conserved not just among the Coronaviridae family members, but across the order Nidovirales. Taken together, these observations suggest that the coronavirus replicative organelle plays an important role in viral replication, perhaps facilitating the production or protection of viral RNA. However, the exact nature of this role, and the specific contexts under which it is important have not been fully elucidated. Here, we collect and interpret the recent experimental evidence about the role and importance of membrane-bound organelles in coronavirus replication.


id: cord-278939-z6kiee09
title: Natural product-derived phytochemicals as potential agents against coronaviruses: a review
author: Mani, Janice S.
date: 2020-04-30
txt: ./txt/cord-278939-z6kiee09.txt
cache: ./cache/cord-278939-z6kiee09.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32360300/
doi: 10.1016/j.virusres.2020.197989
summary:
  As previous work has highlighted the potential of traditional Chinese medicines as a source of potential novel drugs (Ling, 2020) , we have not included details on such studies investigating the antiviral activity of remedies comprising portions of numerous plant species in this review. (2020) virtually screened 83 compounds found in Chinese traditional medicines for activity against the RNA-dependent RNA polymerase of SARS-CoV-2, identifying theaflavin, an antioxidant polyphenol, as a potential inhibitor. Several authors have utilised virtual computer docking models to screen for potential compounds that could bind to and inhibit key proteins present in SARS-CoV (Liu and Zhou, 2005; Toney et al., 2004; Wang et al., 2007) , highlighting the potential antiviral activity of compounds such as sabadinine and aurantiamide acetate. Several large in vitro screening studies searching for inhibitory activity of naturally occurring compounds against SARS-CoV have been performed, mainly on Chinese medicinal herbs (Li et al., 2005; Wang et al., 2003) .

abstract:
  Coronaviruses are responsible for a growing economic, social and mortality burden, as the causative agent of diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), avian infectious bronchitis virus (IBV) and COVID-19. However, there is a lack of effective antiviral agents for many coronavirus strains. Naturally existing compounds provide a wealth of chemical diversity, including antiviral activity, and thus may have utility as therapeutic agents against coronaviral infections. The PubMed database was searched for papers including the keywords coronavirus, SARS or MERS, as well as traditional medicine, herbal, remedy or plants, with 55 primary research articles identified. The overwhelming majority of publications focussed on polar compounds. Compounds that show promise for the inhibition of coronavirus in humans include scutellarein, silvestrol, tryptanthrin, saikosaponin B(2), quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins such as griffithsin. Other compounds such as lycorine may be suitable if a therapeutic level of antiviral activity can be achieved without exceeding toxic plasma concentrations. It was noted that the most promising small molecules identified as coronavirus inhibitors contained a conjugated fused ring structure with the majority being classified as being polyphenols.


id: cord-279827-921kvrrz
title: Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells
author: Murata, Takayuki
date: 1999-06-11
url: https://www.ncbi.nlm.nih.gov/pubmed/10426207/
doi: 10.1016/s0168-1702(99)00023-4
abstract:
  Bovine herpesvirus-1 (BHV-1) can replicate well in bovine-derived cell lines such as Madin Darby bovine kidney (MDBK) but grows poorly in hamster lung (HmLu-1). Virus replication, DNA synthesis, and immediate-early gene expression are severely restricted in HmLu-1. We compared adsorption and penetration of BHV-1 in permissive MDBK and semi-permissive HmLu-1 cells. At a low multiplicity of infection, BHV-1 attached to permissive MDBK cells twice as much as to HmLu-1. The presence of heparin inhibited the attachment of BHV-1 to MDBK cells by about 60%, but over 90% of the attachment was inhibited in HmLu-1. To investigate the penetration of BHV-1, we performed the quantitative measurement of viral DNA by quantitative competitive (QC)PCR in infected cells. In MDBK cells, virions attached to the cell surface, penetrated into the cells and were transported to the nucleus. However in HmLu-1, only a small fraction of the virions attached to the cell surface were allowed to penetrate. Our results indicated that the replication of BHV-1 in semi-permissive HmLu-1 was not dramatically restricted at one certain point but at some various stages including adsorption and penetration.


id: cord-279849-zzkliu76
title: A systematic approach to virus–virus interactions
author: DaPalma, T.
date: 2010-01-20
url: https://doi.org/10.1016/j.virusres.2010.01.002
doi: 10.1016/j.virusres.2010.01.002
abstract:
  A virus–virus interaction is a measurable difference in the course of infection of one virus as a result of a concurrent or prior infection by a different species or strain of virus. Many such interactions have been discovered by chance, yet they have rarely been studied systematically. Increasing evidence suggests that virus–virus interactions are common and may be critical to understanding viral pathogenesis in natural hosts. In this review we propose a system for classifying virus–virus interactions by organizing them into three main categories: (1) direct interactions of viral genes or gene products, (2) indirect interactions that result from alterations in the host environment, and (3) immunological interactions. We have so far identified 15 subtypes of interaction and assigned each to one of these categories. It is anticipated that this framework will provide for a more systematic approach to investigating virus–virus interactions, both at the cellular and organismal levels.


id: cord-279969-5nlmljcw
title: Sequence analysis of the N, P, M and F genes of Canadian human metapneumovirus strains()
author: Bastien, Nathalie
date: 2003-04-03
url: https://www.sciencedirect.com/science/article/pii/S0168170203000650
doi: 10.1016/s0168-1702(03)00065-0
abstract:
  The complete nucleotide sequences of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) genes of 15 Canadian human metapneumovirus (hMPV) isolates were determined. Phylogenetic analysis revealed two distinct genetic clusters, or groups for each gene with additional sequence variability within the individual groups. Comparison of the deduced amino acid sequences for the N, M and F genes of the different isolates revealed that all three genes were well conserved with 94.1–97.6% identity between the two distinct clusters The P gene showed more diversity with 81.6–85.7% amino acid identity for isolates between the two clusters, and 94.6–100% for isolates within the same cluster.


id: cord-280643-n8qjorqk
title: Inhibition of Hepatitis B virus gene expression by single and dual small interfering RNA treatment
author: Wu, Kai-Lang
date: 2005-04-26
txt: ./txt/cord-280643-n8qjorqk.txt
cache: ./cache/cord-280643-n8qjorqk.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170205000948
doi: 10.1016/j.virusres.2005.04.001
summary:
  To circumvent the problem that mutation in HBV genome may result in resistance when siRNA is further developed as an anti-viral drug, in this study, we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules that can specifically target two genes. To test the effectiveness of this system, we applied this new approach to express simultaneously two different 21-bp hairpin siRNA duplexes that specifically attack the HBs and HBx genes of HBV, respectively, in Bel-7402 and HepG2.2.15 cells. Results indicated that dual siRNA could simultaneously inhibit the expression of HBs and HBx gene by 83.7% and 87.5%, respectively, based on luciferase assays. Results indicated that the levels of HBV core associ-ated DNA were significantly decreased in the cells transfected by HBSXsiRNA, HBS 1 siRNA, HBS 2 siRNA, and HBX 2 siRNA with reduction rate of 90.2%, 85.7 %, 81.3%, and 60.4%, respectively, compared with that of vector control (Fig. 5a) .

abstract:
  RNA interference (RNAi) has been successfully applied in suppression of Hepatitis B virus (HBV) replication. To circumvent the problem that mutation in HBV genome may result in resistance when siRNA is further developed as an anti-viral drug, in this study, we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules that can specifically target two genes. To test the effectiveness of this system, we applied this new approach to express simultaneously two different 21-bp hairpin siRNA duplexes that specifically attack the HBs and HBx genes of HBV, respectively, in Bel-7402 and HepG2.2.15 cells. Results indicated that dual siRNA could simultaneously inhibit the expression of HBs and HBx gene by 83.7% and 87.5%, respectively, based on luciferase assays. In addition, dual siRNA molecules were able to significantly reduce the amount of HBV core associated DNA, which is considered as an intracellular replicative intermediate, and the viral DNA in culture supernatant. Therefore, this dual siRNA system provides a more powerful tool for the study of gene function and implicates a potential application in the treatment of viral infection.


id: cord-281101-gv1sgbk1
author: Shin, Gu-Choul
date: 2006-08-30
url: https://www.ncbi.nlm.nih.gov/pubmed/16942813/
doi: 10.1016/j.virusres.2006.07.004
title:
  Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein

abstract:
  Severe acute respiratory syndrome-coronavirus nucleocapsid (SARS-CoV N) protein has been found to be important to the processes related to viral pathogenesis, such as virus replication, interference of the cell process and modulation of host immune response; detection of the antigen has been used for the early diagnosis of infection. We have used recombinant N protein expressed in insect cells to generate 17 mAbs directed against this protein. We selected five mAbs that could be used in various diagnostic assays, and all of these mAbs recognized linear epitopes. Three IgG(2b) mAbs were recognized within the N-terminus of N protein, whereas the epitope of two IgG(1) mAbs localized within the C-terminus. These mAbs were found to have significant reactivity with both non-phosphorylated and phosphorylated N proteins, which resulted in high reactivity with native N protein in virus-infected cells; however, they did not show cross-reactivity with human coronavirus. Therefore, these results suggested that these mAbs would be useful in the development of various diagnostic kits and in future studies of SARS-CoV pathology.


id: cord-281526-7t9e4lgn
author: Yin, Lijuan
date: 2016-09-02
txt: ./txt/cord-281526-7t9e4lgn.txt
cache: ./cache/cord-281526-7t9e4lgn.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S016817021630274X
doi: 10.1016/j.virusres.2016.07.010
summary:
  title: Immunogenicity and protective efficacy of recombinant fusion proteins containing spike protein of infectious bronchitis virus and hemagglutinin of H3N2 influenza virus in chickens To investigate whether the recombinant proteins could induce better immune response against IBV infection, we detected IBVspecific antibody in the sera of vaccinated chicken using indirect ELISA. Two weeks after booster vaccination (day 28), the levels of anti-IBV antibodies increased further in chickens immunized with inactivated M41 virus, rS1, rS1-H3(TM) and rS1-HA2. After challenged with virulent IBV M41 strain, our results demonstrated that fusion proteins performed better protection compared with inactivated M41 vaccine and recombinant rS1 protein alone, while the latter groups presented similar protection ratio. The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus

title:
  Immunogenicity and protective efficacy of recombinant fusion proteins containing spike protein of infectious bronchitis virus and hemagglutinin of H3N2 influenza virus in chickens

abstract:
  Infectious bronchitis (IB) is an acute and highly contagious viral respiratory disease of chickens and vaccination is the main method for disease control. The S1 protein, which contains several virus neutralization epitopes, is considered to be a target site of vaccine development. However, although protective immune responses could be induced by recombinant S1 protein, the protection rate in chickens was still low (<50%). Here, we generated fused S1 proteins with HA2 protein (rS1-HA2) or transmembrane domain and cytoplasmic tail (rS1-H3(TM)) from hemagglutinin of H3N2 influenza virus. After immunization, animals vaccinated with fusion proteins rS1-HA2 and rS1-H3(TM) demonstrated stronger robust humoral and cellular immune responses than that of rS1 and inactivated M41 vaccine. The protection rates of groups immunized with rS1-HA2 (87%) were significantly higher than the groups inoculated with rS1 (47%) and inactivated M41 vaccine (53%). And chickens injected with rS1-H3(TM) had similar level of protection (73%) comparing to chickens vaccinated with rS1 (47%) (P = 0.07). Our data suggest that S1 protein fused to the HA2 or TM proteins from hemagglutinin of H3N2 influenza virus may provide a new strategy for high efficacy recombinant vaccine development against IBV.


id: cord-284479-75zgljet
title: Drug repurposing for new, efficient, broad spectrum antivirals
author: García-Serradilla, Moisés
date: 2019-04-15
txt: ./txt/cord-284479-75zgljet.txt
cache: ./cache/cord-284479-75zgljet.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2019.02.011
doi: 10.1016/j.virusres.2019.02.011
summary:
  Thus, the antiviral activity of cyclosporine A (CsA) and some of its nonimmunosuppressive analogs against these viruses has been shown to be related to its ability to bind cellular cyclophilins and inhibiting the interaction with the viral proteins (Bienkowska-Haba et al., 2009; Bose et al., 2003; Damaso and Moussatche, 1998; Franke et al., 1994; Kaul et al., 2009; Nakagawa et al., 2004; Thali et al., 1994; Wainberg et al., 1988; Yang et al., 2008) . CsA has also been reported to inhibit the propagation of several strains of influenza A virus in cell cultures blocking a late step of the replication cycle by mechanisms that might implicate CypA-dependent and -independent pathways (Hamamoto et al., 2013; Liu et al., 2012a; Ma et al., 2016) . Therefore, further studies are needed to better understand the mode of action of AgNPs, their cell specificity and toxicological issues in order to generate new and more effective compounds as well as the use in combination with other drugs in the treatment of different viral diseases.

abstract:
  Emerging viruses are a major threat to human health. Recent outbreaks have emphasized the urgent need for new antiviral treatments. For several pathogenic viruses, considerable efforts have focused on vaccine development. However, during epidemics infected individuals need to be treated urgently. High-throughput screening of clinically tested compounds provides a rapid means to identify undiscovered, antiviral functions for well-characterized therapeutics. Repurposed drugs can bypass part of the early cost and time needed for validation and authorization. In this review we describe recent efforts to find broad spectrum antivirals through drug repurposing. We have chosen several candidates and propose strategies to understand their mechanism of action and to determine how resistance to antivirals develops in infected cells.


id: cord-284866-66azyje4
title: A detailed comparative analysis on the overall codon usage patterns in Hepatitis A virus
author: D’ Andrea, Lucía
date: 2011-02-04
txt: ./txt/cord-284866-66azyje4.txt
cache: ./cache/cord-284866-66azyje4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2011.01.012
doi: 10.1016/j.virusres.2011.01.012
summary:
  The first axis in COA is highly correlated with the GC 3 S and GC 12 values in HAV ORFs. This result reveals that nucleotide composition plays an important key role in the codon usage bias observed in HAV ORFs (see Table 2 ). These observations indicate that the composition of dinucleotides also plays a key role in the variation found in synonymous codon usage among HAV ORFs. To study the possible effects of CpG under-representation on codon usage bias of HAV ORFs, the RSCU value of the eight codons that contain CpG (CCG, GCG, UCG, ACG, CGC, CGG, CGU, CGA) were analyzed. The results of these studies revealed that codon usage in HAV ORFs is quite different from that of human genes (see Table 1 ). Positions of the 30 HAV ORFs in the plot of the first two major axes by correspondence analysis (COA) of relative synonymous codon usage (RSCU) values.

abstract:
  Hepatitis A virus (HAV) is a hepatotropic member of the family Picornaviridae. HAV has several unique biological characteristics that distinguish it from other members of this family. Recent and previous studies revealed that codon usage plays a key role in HAV replication and evolution. In this study, the patterns of synonymous codon usage in HAV have been studied through multivariate statistical methods on 30 complete open reading frames (ORFs) from the available 30 full-length HAV sequences. Effective number of codons (ENC) indicates that the overall extent of codon usage bias in HAV genomes is significant. The relative dinucleotide abundances suggest that codon usage in HAV can also be strongly influenced by underlying biases in dinucleotide frequencies. These factors strongly correlated with the first major axis of correspondence analysis (COA) on relative synonymous codon usage (RSCU). The distribution of the HAV ORFs along the plane defined by the first two major axes in COA showed that different genotypes are located at different places in the plane, suggesting that HAV codon usage is also reflecting an evolutionary process. It has been very recently described that fine-tuning translation kinetics selection also contributes to codon usage bias of HAV. The results of these studies suggest that HAV genomic biases are the result of the co-evolution of genome composition, controlled translation kinetics and probably the ability to escape the antiviral cell responses.


id: cord-285180-32bxx94u
author: Lee, Sunhee
date: 2015-10-02
url: https://api.elsevier.com/content/article/pii/S0168170215002786
doi: 10.1016/j.virusres.2015.06.013
title:
  Functional characterization and proteomic analysis of the nucleocapsid protein of porcine deltacoronavirus

abstract:
  Porcine deltacoronavirus (PDCoV) is a newly discovered enterotropic swine coronavirus that causes enteritis and diarrhea in piglets. Like other coronaviruses, PDCoV commonly contains 4 major structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Among these, the N protein is known to be the most abundant and multifunctional viral component. Therefore, as the first step toward understanding the biology of PDCoV, the present study investigated functional characteristics and expression dynamics of host proteins in a stable porcine cell line constitutively expressing the PDCoV N protein. Similar to N proteins of other coronaviruses, the PDCoV N protein was found to interact with itself to form non-covalently linked oligomers and was mainly localized to the nucleolus. We then assessed alterations in production levels of proteins in the N-expressing PK (PK-PDCoV-N) cells at different time points by means of proteomic analysis. According to the results of high-resolution two-dimensional gel electrophoresis, a total of 43 protein spots were initially found to be differentially expressed in PK-PDCoV-N cells in comparison with control PK cells. Of these spots, 10 protein spots showed a statistically significant alteration, including 8 up-regulated and 2 down-regulated protein spots and were picked for subsequent protein identification by peptide mass fingerprinting following matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The affected cellular proteins that we identified in this study were classified into the functional groups involved in various cellular processes such as cell division, metabolism, the stress response, protein biosynthesis and transport, cytoskeleton networks and cell communication. Notably, two members of the heat shock protein 70 family were found to be up-regulated in PK-PDCoV-N cells. These proteomic data will provide insights into the specific cellular response to the N protein during PDCoV infection.


id: cord-285580-gq7400tq
author: Pieretti, Joana C.
date: 2020-10-18
txt: ./txt/cord-285580-gq7400tq.txt
cache: ./cache/cord-285580-gq7400tq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2020.198202
doi: 10.1016/j.virusres.2020.198202
summary:
  In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. Although positive biological effects have been reported for the administration of NO donors, further studies are required to better evaluate the levels of inflammatory mediators and the activity of important heme-containing enzymes, such as indoleamine 2,3-dioxygenase (IDO), directly involved in the inflammatory responses in respiratory viral infections (Anderson and Russel, 2020) . In other words, NO demonstrates potential for the treatment of patients infected with COVID-19 both in severe and nonsevere conditions, improving oxygenation and antiviral mechanisms, and preventing aggravation of the disease (Ferrari et al., 2020; Parikh et al., 2020) . Protocol of a randomized controlled trial testing inhaled nitric oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2)

title:
  Nitric oxide (NO) and nanoparticles – potential small tools for the war against COVID-19 and other human coronavirus infections

abstract:
  The endogenous free radical nitric oxide (NO) plays a pivotal role in the immunological system. NO has already been reported as a potential candidate for use in the treatment of human coronavirus infections, including COVID-19. In fact, inhaled NO has been used in clinical settings for its antiviral respiratory action, and in the regulation of blood pressure to avoid clot formation. In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. We also highlight promising therapeutic effects of NO donors allied to nanomaterials to combat COVID-19 and other human coronavirus infections. Nanomaterials can be designed to deliver sustained, localized NO release directly at the desired application site, enhancing the beneficial effects of NO and minimizing the side effects. Challenges and perspectives are presented to open new fields of research.


id: cord-286416-8eu6wp9b
title: Viral modulation of stress granules
author: Valiente-Echeverría, Fernando
date: 2012-06-14
txt: ./txt/cord-286416-8eu6wp9b.txt
cache: ./cache/cord-286416-8eu6wp9b.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170212002018
doi: 10.1016/j.virusres.2012.06.004
summary:
  If deadenylation (e.g., CCR4/Not1), destabilization (e.g., TTP/XRN1) and decapping (e.g., DCP1/DCP2) complex; and even RISC (Ago) complex are recruited to mRNA, these will be targeted to PBs. Conversely, if TIA-1/TIAR or proteins such as G3BP/USP10 are recruited to the stalled initiation complexes, these will be directed to SGs. Different pathways in SG assembly are described (in red): (i) phosphorylation of eIF2␣ induced by the exposure to different stress inducers (e.g., arsenite and thapsigargin) (Fig. 1) ; (ii) Hippuristanol and Pateamine A, drugs that inhibit the helicase activity of eIF4A altering ATP binding or ATPase activity; and (iii) the overexpression of SG markers, such as G3BP or TIA-1. West Nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly

abstract:
  Following viral infection, the host responds by mounting a robust anti-viral response with the aim of creating an unfavorable environment for viral replication. As a countermeasure, viruses have elaborated mechanisms to subvert the host response in order to maintain viral protein synthesis and production. In the last decade, several reports have shown that viruses modulate the assembly of stress granules (SGs), which are translationally silent ribonucleoproteins (RNPs) and sites of RNA triage. This review discusses recent advances in our understanding of the interactions between viruses and the host response and how virus-induced modulations in SG abundance play fundamental roles in dictating the success of viral replication.


id: cord-286473-sl5zy8nj
title: Complete genomic sequence of turkey coronavirus
author: Gomaa, M.H.
date: 2008-05-12
url: https://api.elsevier.com/content/article/pii/S0168170208001317
doi: 10.1016/j.virusres.2008.03.020
abstract:
  Turkey coronavirus (TCoV), one of the least characterized of all known coronaviruses, was isolated from an outbreak of acute enteritis in young turkeys in Ontario, Canada, and the full-length genomic sequence was determined. The full-length genome was 27,632 nucleotides plus the 3′ poly(A) tail. Two open reading frames, ORFs 1a and 1b, resided in the first two thirds of the genome, and nine additional downstream ORFs were identified. A gene for hemagglutinin-esterase was absent in TCoV. The region between the membrane (M) and nucleocapsid (N) protein genes contained three potential small ORFs: ORF-X, a previously uncharacterized ORF with an associated putative TRS within the M gene (apparently shared among all group III coronaviruses), and previously described ORFs 5a and 5b. The TCoV genome is organized as follows: 5′ UTR – replicase (ORFs 1a, 1b) – spike (S) protein – ORF3 (ORFs 3a, 3b) – small envelop (E or 3c) protein – membrane (M) protein – ORF5 (ORFs X, 5a, 5b) – nucleocapsid (N) protein −3′ UTR – poly(A). TCoV genome structure and sequence was most similar, but distinct from, avian infectious bronchitis virus (IBV). This is the first complete genome sequence for a TCoV and confirms that TCoV belongs to group III coronaviruses.


id: cord-286658-9kco7qad
author: Jiang, Lei
date: 2018-01-15
txt: ./txt/cord-286658-9kco7qad.txt
cache: ./cache/cord-286658-9kco7qad.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170217307098
doi: 10.1016/j.virusres.2017.11.007
summary:
  Recently, numerous IBV strains have been identified and new genotypes/serotypes have emerged from existing viruses via point mutations, insertions, and deletions in the viral genome, especially in the S1 subunit of the spike protein gene. There have been several episodes of infectious bronchitis (IB) in Chinese chicken flocks, and the genotypes/serotypes of IBVs were previously classified based mainly on the nucleotide sequences of genes encoding the S1 subunit of the spike protein (Han et al., 2011) , and in some cases based on cross virus-neutralization Chen et al., 2017) in China. In addition, it is very interesting to note that the/I1101/16 isolate exhibited decreased replication levels in both the tracheal and kidney tissues (two target tissues for most IBVs) compared with one of its parental viruses (the ck/CH/LHLJ/140901 strain, which does not cause severe clinical disease in SPF chickens), but it exhibited prolonged replication and shedding post-challenge in a Table 3 Pairwise comparisons of the nucleotide sequences of the S2 subunit of the spike genes between the 4/91 vaccine strain, I1101/16 isolate, and pathogenic 4/91 strain a .

title:
  Characterization of the complete genome, antigenicity, pathogenicity, tissue tropism, and shedding of a recombinant avian infectious bronchitis virus with a ck/CH/LJL/140901-like backbone and an S2 fragment from a 4/91-like virus

abstract:
  In this study, we isolated an infectious bronchitis virus, designated I1101/16, from broiler breeders in China. Analysis of the S1 gene showed that isolate I1101/16 was genetically close to strain ck/CH/LJL/140901, which belongs to the TW I genotype (also known as lineage GI-7 based on the recent IBV classification), however the S2 gene showed genetic diversity comparing to that of S1 gene. Comparison of the genomic sequences showed that the genome of isolate I1101/16 was similar to that of strain ck/CH/LJL/140901 from the 5′ end of the genome to the 5′ end of the S2 gene and from the 5′ end of the 3a gene to the end of the genome, whereas the remaining parts of the genome sequences were more closely related to those of strain 4/91 than those of ck/CH/LJL/140901, thereby suggesting that recombination might have occurred during the origin of the virus. SimPlot and Bootscan analysis of the complete genomic sequence confirmed this hypothesis, where it showed that isolate I1101/16 arose through recombination events between ck/CH/LJL/140901- and 4/91-like viruses. Isolate I1101/16 and strain ck/CH/LJL/140901 shared identical amino acids in almost all five of their B cell epitopes, but the two viruses had a serotype relatedness value of 65, which is well below 80, i.e., the lower cutoff value for viruses of the same serotype. In addition, pathogenicity tests demonstrated that isolate I1101/16 was more pathogenic to 1-day-old specific-pathogen-free chickens than strain ck/CH/LJL/140901, according to analysis of the clinical signs, whereas strain ck/CH/LJL/140901 exhibited prolonged replication and shedding after challenge compared with isolate I1101/16. This study did not provide evidence that recombination can directly alter the antigenicity, virulence, replication, shedding, and tissue tropism of a virus, but it did show that recombination events are likely to be major determinants of viral evolution.


id: cord-286703-ipoj13va
author: de Wilde, Adriaan H.
date: 2017-01-15
txt: ./txt/cord-286703-ipoj13va.txt
cache: ./cache/cord-286703-ipoj13va.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27840112/
doi: 10.1016/j.virusres.2016.11.011
summary:
  Data from cell culture infection models (Chan et al., 2013a (Chan et al., , 2013b de Wilde et al., 2013b; Falzarano et al., 2013a; Kindler et al., 2013; Zielecki et al., 2013) and experiments in rhesus macaques (Falzarano et al., 2013b) and marmosets (Chan et al., 2015) suggested that interferons (IFNs) are potent inhibitors of MERS-CoV replication. As ribavirin has previously been reported to inhibit MERS-CoV replication (Falzarano et al., 2013a) and ALV and ribavirin have been used together during clinical trials for hepatitis C treatment (Pawlotsky et al., 2015) , this combination was tested in LLC-MK2 cells. (e, f) SARS-CoV-infected (e) Vero or (f) VeroE6 cells (MOI 0.01) were treated with various concentrations of ALV from 1 h p.i. onwards, and virus titers in the culture medium at 32 h p.i. were determined by plaque assay.

title:
  Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model

abstract:
  Currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication.


id: cord-287324-ecpicv5v
author: Qiu, Yuan
date: 2017-06-02
txt: ./txt/cord-287324-ecpicv5v.txt
cache: ./cache/cord-287324-ecpicv5v.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170217302150
doi: 10.1016/j.virusres.2017.05.003
summary:
  In this study, we detected the viromes of RNA viruses of one mock sample, one pooled duck feces sample and one pooled mink feces sample on the Personal Genome Machine platform using the sequencing libraries prepared by three methods. In this study, we detected the viromes of RNA viruses of one mock sample and two pooled authentic samples, using the libraries prepared by the three methods on the Personal Genome Machine (PGM) platform, with the aim to generate data of significance for virome detection of RNA viruses and characterize the viromes of RNA viruses in ducks and minks. In the future, it is of significance to compare methods 2 and 3 in detecting viromes of RNA viruses in some clinical samples containing limited viral RNA. Detection of viromes of ducks and minks increases our understanding of the viral diversity in the animals, and provides novel clues for further studies regarding diagnosis of infectious diseases, identification of novel viruses and research of host-virus relationships.

title:
  Detection of viromes of RNA viruses using the next generation sequencing libraries prepared by three methods

abstract:
  Virome (viral megagenomics) detection using next generation sequencing has been widely applied in virology, but its methods remain complicated and need optimization. In this study, we detected the viromes of RNA viruses of one mock sample, one pooled duck feces sample and one pooled mink feces sample on the Personal Genome Machine platform using the sequencing libraries prepared by three methods. The sequencing primers were added through random hybridization and ligation to fragmented viral RNA using a RNA-Seq kit in method 1, through random reverse transcription (RT) and polymerase chain reaction (PCR) in method 2 which was developed in our laboratory, and through hybridization and ligation to fragmented amplicons of random RT-PCR using a single primer in method 3. Although the results of these three samples (nine libraries) all showed that more classified viral families and genera were identified using methods 2 and 3 than using method 1, and more classified viral families and genera were identified using method 2 than using method 3, most of the differences were of no statistical significance. Moreover, 11 mammalian viral genera in minks were possibly identified for the first time through this study.


id: cord-288253-wqrhiq08
author: Park, Jung-Eun
date: 2015-02-02
txt: ./txt/cord-288253-wqrhiq08.txt
cache: ./cache/cord-288253-wqrhiq08.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2014.12.024
doi: 10.1016/j.virusres.2014.12.024
summary:
  Because the major pathological changes of the porcine coronaviruses (e.g., TGEV and PEDV) involves enteric diseases, we measured porcine APN expression in the small intestine by RT-PCR, immunoblotting, and IHC. An immunohistochemical analysis, with both anti-Flag and anti-porcine APN antibodies, clearly confirmed porcine APN expression in the brush borders of the absorptive cells in the small intestines of the mouse model (Fig. 4C) . For these purposes, many transgenic mouse models have been developed to study viral pathogenesis, immune responses, and vaccines (Darling et Both wild type and porcine APN transgenic mice were infected with PEDV (5X TCID5010 6 ) orally on day 0. Although significant clinical illness was not observed when the transgenic mice were infected with PEDV, their susceptibility to the virus was confirmed by the detection of viral RNA in various organs with RT-PCR and viral proteins in the small intestines with IHC.

title:
  Development of transgenic mouse model expressing porcine aminopeptidase N and its susceptibility to porcine epidemic diarrhea virus

abstract:
  Porcine coronavirus infections have known as they are specific to pigs with predominantly enteric or respiratory diseases. No laboratory animal model is yet been developed in porcine coronaviruses study. Here, we report that development of a transgenic mouse model expressing porcine APN which is susceptible to porcine coronavirus infection. The porcine APN transgene was constructed by fusing with mouse proximal APN promoter at 5′ terminus and bovine growth hormone polyadenylation site at its 3′ terminus. After screen on pubs from the microinjected mice, we confirmed two transgenic lines expressing porcine APN in various organs. We confirmed the susceptibility to porcine epidemic diarrhea virus, one of the porcine coronaviruses. These transgenic mice will be an important tool for research into the porcine coronaviruses.


id: cord-290481-i2ppvsh5
title: Comparative and functional genomics of closteroviruses
author: Dolja, Valerian V.
date: 2006-03-09
txt: ./txt/cord-290481-i2ppvsh5.txt
cache: ./cache/cord-290481-i2ppvsh5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16529837/
doi: 10.1016/j.virusres.2006.02.002
summary:
  It was concluded that, at least in part, viral pathogenicity is due to interference of silencing suppressors with developmental function of plant small RNAs. Despite their mechanistic similarity, p21 and p19 appear to be structurally and evolutionarily unrelated and neither has detectable homologues outside the respective virus genera (Vargason et al., 2003; Ye and Patel, 2005) . Although Citrus tristeza virus (CTV) encodes p20, a p21like suppressor of RNA silencing, screening of the CTV genome revealed an additional suppressor, p23, that has no homologues in other closteroviruses (Fig. 2) (Lu et al., 2004) . A comparison of TMV and BYV, which both evolved from the alphavirus-like ancestors, shows that the large part of the ∼9 kb genomic surplus of BYV is dedicated to facilitating the synthesis of the virion RNA and multiple sgRNAs. The rest of the surplus was invested in the formation of the complex virion tail that empowers virus transport within and transmission between the host plants and in suppression of RNA silencing (Fig. 1) .

abstract:
  The largest extant RNA genomes are found in two diverse families of positive-strand RNA viruses, the animal Coronaviridae and the plant Closteroviridae. Comparative analysis of the viruses from the latter family reveals three levels of gene conservation. The most conserved gene module defines RNA replication and is shared with plant and animal viruses in the alphavirus-like superfamily. A module of five genes that function in particle assembly and transport is a hallmark of the family Closteroviridae and was likely present in the ancestor of all three closterovirus genera. This module includes a homologue of Hsp70 molecular chaperones and three diverged copies of the capsid protein gene. The remaining genes show dramatic variation in their numbers, functions, and origins among closteroviruses within and between the genera. Proteins encoded by these genes include suppressors of RNA silencing, RNAse III, papain-like proteases, the AlkB domain implicated in RNA repair, Zn-ribbon-containing protein, and a variety of proteins with no detectable homologues in the current databases. The evolutionary processes that have shaped the complex and fluid genomes of the large RNA viruses might be similar to those that have been involved in evolution of genomic complexity in other divisions of life.


id: cord-290801-dv6aak01
title: Reprint of: Core protein-mediated 5′–3′ annealing of the West Nile virus genomic RNA in vitro()
author: Ivanyi-Nagy, Roland
date: 2012-09-27
txt: ./txt/cord-290801-dv6aak01.txt
cache: ./cache/cord-290801-dv6aak01.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170212003279
doi: 10.1016/j.virusres.2012.09.009
summary:
  Since the core protein of flaviviruses is also endowed with potent RNA chaperone activities, we decided to examine the effect of West Nile virus (WNV) core on 5′–3′ genomic RNA annealing in vitro. These results indicate that core protein – besides its function in viral particle formation – might be involved in the regulation of flavivirus genomic RNA cyclization, and thus virus replication. In this study, we examined the effect of WNV core protein chaperoning on viral 5 -3 UTR annealing, using an in vitro model system with separate 5 and 3 RNAs. We found that core protein binding greatly increases the rate of 5 -3 complex formation, and is required for the interaction when full-length 3 UTR RNAs are used (Fig. 2) .

abstract:
  Genome cyclization through conserved RNA sequences located in the 5′ and 3′ terminal regions of flavivirus genomic RNA is essential for virus replication. Although the role of various cis-acting RNA elements in panhandle formation is well characterized, almost nothing is known about the potential contribution of protein cofactors to viral RNA cyclization. Proteins with nucleic acid chaperone activities are encoded by many viruses (e.g., retroviruses, coronaviruses) to facilitate RNA structural rearrangements and RNA–RNA interactions during the viral replicative cycle. Since the core protein of flaviviruses is also endowed with potent RNA chaperone activities, we decided to examine the effect of West Nile virus (WNV) core on 5′–3′ genomic RNA annealing in vitro. Core protein binding resulted in a dramatic, dose-dependent increase in 5′–3′ complex formation. Mutations introduced in either the UAR (upstream AUG region) or CS (conserved sequence) elements of the viral RNA diminished core protein-dependent annealing, while compensatory mutations restored the 5′–3′ RNA interaction. The activity responsible for stimulating RNA annealing was mapped to the C-terminal RNA-binding region of WNV core protein. These results indicate that core protein – besides its function in viral particle formation – might be involved in the regulation of flavivirus genomic RNA cyclization, and thus virus replication.


id: cord-290948-cuu78cvl
title: The SARS-Coronavirus PLnc domain of nsp3 as a replication/transcription scaffolding protein
author: Imbert, Isabelle
date: 2008-02-05
txt: ./txt/cord-290948-cuu78cvl.txt
cache: ./cache/cord-290948-cuu78cvl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2007.11.017
doi: 10.1016/j.virusres.2007.11.017
summary:
  Using the combination of yeast two-hybrid screening and GST pull-down assays, we have now analyzed all potential interactions between SARS-Coronavirus nonstructural proteins, which may contribute to the structure and/or function of the viral replication/transcription complex. SARS-CoV nsp3 is a large multidomain protein of 1922 amino acids Thiel et al., 2003) that is thought to contain at least seven domains: (1) an N-terminal Glu-rich acidic domain (AD); (2) an X domain (XD) with poly(ADP-ribose) binding properties Saikatendu et al., 2005) ; (3) the SUD domain (for SARS-CoV Unique Domain, an insertion not found in any other coronavirus thus far) with a specific affinity for oligo(G)-strings (Tan et al., in press); (4) a papain-like protease (PLP2), recently shown to exhibit deubiquitinating activity (Barretto et al., 2005; Harcourt et al., 2004; Lindner et al., 2005; Ratia et al., 2006) ; (5) an unknown domain possibly extending the papain-like protease domain, termed PLnc for Papain-Like noncanonical (see below); (6) a transmembrane domain (Kanjanahaluethai et al., 2007) corresponding to the N-terminal of the Y domain; and (7) the remainder of the Y domain, the abbreviation "Y domain" will be used for this part in this study.

abstract:
  Many genetic and mechanistic features distinguish the coronavirus replication machinery from that encoded by most other RNA viruses. The coronavirus replication/transcription complex is an assembly of viral and, most probably, cellular proteins that mediate the synthesis of both the unusually large (∼30 kb) RNA genome and an extensive set of subgenomic mRNAs. The viral components of the complex are encoded by the giant replicase gene, which is expressed in the form of two polyproteins (pp1a and pp1ab) that are processed into 16 cleavage products (nonstructural proteins 1–16). Using the combination of yeast two-hybrid screening and GST pull-down assays, we have now analyzed all potential interactions between SARS-Coronavirus nonstructural proteins, which may contribute to the structure and/or function of the viral replication/transcription complex. We demonstrate the existence of a complex network of interactions involving all 16 nonstructural proteins. Our results both confirmed previously described associations and identified novel heterodimerizations. The interaction map thus provides a sum of the interactions that may occur at some point during coronavirus RNA synthesis and provides a framework for future research.


id: cord-291086-goidlh08
title: Rhabdovirus accessory genes
author: Walker, Peter J.
date: 2011-09-14
url: https://www.ncbi.nlm.nih.gov/pubmed/21933691/
doi: 10.1016/j.virusres.2011.09.004
abstract:
  The Rhabdoviridae is one of the most ecologically diverse families of RNA viruses with members infecting a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The availability of complete nucleotide sequences for an increasing number of rhabdoviruses has revealed that their ecological diversity is reflected in the diversity and complexity of their genomes. The five canonical rhabdovirus structural protein genes (N, P, M, G and L) that are shared by all rhabdoviruses are overprinted, overlapped and interspersed with a multitude of novel and diverse accessory genes. Although not essential for replication in cell culture, several of these genes have been shown to have roles associated with pathogenesis and apoptosis in animals, and cell-to-cell movement in plants. Others appear to be secreted or have the characteristics of membrane-anchored glycoproteins or viroporins. However, most encode proteins of unknown function that are unrelated to any other known proteins. Understanding the roles of these accessory genes and the strategies by which rhabdoviruses use them to engage, divert and re-direct cellular processes will not only present opportunities to develop new anti-viral therapies but may also reveal aspects of cellar function that have broader significance in biology, agriculture and medicine.


id: cord-291754-1zxztadu
author: Zhao, Ye
date: 2019-10-15
txt: ./txt/cord-291754-1zxztadu.txt
cache: ./cache/cord-291754-1zxztadu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31430502/
doi: 10.1016/j.virusres.2019.197726
summary:
  In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. To compare the in vitro replication of the rescued virus rYN and its parental strain YN on CEK cells, 200 μl PBS containing 10 3.0 TCID 50 of rYN or YN virus were inoculated onto the CEK cells in 24-well plates, and 200 μl supernatants from three wells from each group were harvested at the time points of 6, 12, 24, 36, 48, and 60 hpi for a real-time PCR detection assay for IBV N gene as described above. Collectively, these results demonstrate the successful rescue of the pathogenic IBV strain YN from cloned cDNA by using electroporation of full-length IBV in vitro transcripts into N-protein expressing cells and subsequent virus amplification in the allantoic cavities of ECE.

title:
  Successful establishment of a reverse genetic system for QX-type infectious bronchitis virus and technical improvement of the rescue procedure

abstract:
  In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. Ten fragments contiguously spanning the complete IBV genome were amplified and cloned into the vaccinia virus genome by homologous recombination. The full-length genomic cDNA was transcribed in vitro, and its transcript was transfected into BHK-21/N cells that could stably express IBV N protein. At 48 h post transfection, the culture medium was harvested and inoculated into 10-day-old specific-pathogen-free embryonated chicken eggs to replicate the rescued virus. This strategy was chosen to facilitate the rescue procedure and to ensure that the recombinant rYN virus will not require any cell culture adaptations. After only one in ovo passage, the recombinant YN virus (rYN) was successfully recovered and confirmed to possess the introduced silent marker mutation in its genome. Biological characteristics of rYN such as the EID(50), TCID(50), replication in ovo, and replication kinetcs in vitro were tested and all were similar to its parental strain YN. Our findings demonstrate the successful construction of highly-pathogenic QX-type IBV using a modified rescue procedure, allowing for future studies of the molecular biology and pathogenicity of IBV field strains.


id: cord-291962-rp172ugk
author: Jing, Huiyuan
date: 2019-07-15
txt: ./txt/cord-291962-rp172ugk.txt
cache: ./cache/cord-291962-rp172ugk.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170219302485
doi: 10.1016/j.virusres.2019.05.011
summary:
  title: Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9 To test this, increasing dose of NLRX1 was transfected into Marc-145 cells followed by PRRSV infection, qPCR was then performed to test the total viral RNA levels. On the other hand, recent literature indicated that the interaction of Nsp9 with SUMO E2 conjugating enzyme Ubc9 and cellular protein interleukin-2 enhancer binding factor 2 (ILF2) through its RdRp domain resulted in a significantly decrease of virus titers, indicating that cells utilize host antiviral factors as defense mechanisms to limit PRRSV infection Wen et al., 2017) . An intracellularly expressed Nsp9-specific nanobody in MARC-145 cells inhibits porcine reproductive and respiratory syndrome virus replication Porcine reproductive and respiratory syndrome virus nucleocapsid protein interacts with Nsp9 and cellular DHX9 to regulate viral RNA synthesis The DEADbox RNA helicase 5 positively regulates the replication of porcine reproductive and respiratory syndrome virus by interacting with viral Nsp9 in vitro

title:
  Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9

abstract:
  Porcine reproductive and respiratory syndrome virus (PRRSV) causes one of the most economically important diseases of swine worldwide. Current antiviral strategies provide only limited protection. Nucleotide-binding oligomerization domain-like receptor (NLR) X1 is unique among NLR proteins in its functions as a pro-viral or antiviral factor to different viral infections. To date, the impact of NLRX1 on PRRSV infection remains unclear. In this study, we found that PRRSV infection promoted the expression of NLRX1 gene. In turn, ectopic expression of NLRX1 inhibited PRRSV replication in Marc-145 cells, whereas knockdown of NLRX1 enhanced PRRSV propagation in porcine alveolar macrophages (PAMs). Mechanistically, NLRX1 was revealed to impair intracellular viral subgenomic RNAs accumulation. Finally, Mutagenic analyses indicated that the LRR (leucine-rich repeats) domain of NLRX1 interacted with PRRSV Nonstructural Protein 9 (Nsp9) RdRp (RNA-dependent RNA Polymerase) domain and was necessary for antiviral activity. Thus, our study establishes the role of NLRX1 as a new host restriction factor in PRRSV infection.


id: cord-293562-69nnyq8p
author: Imran, Mudassar
date: 2018-08-15
txt: ./txt/cord-293562-69nnyq8p.txt
cache: ./cache/cord-293562-69nnyq8p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30003923/
doi: 10.1016/j.virusres.2018.07.002
summary:
  We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R 0 < 1. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R 0 < 1. Since the only way to control the disease is to isolate patients who have been infected with the Zika virus, we included a new population compartment consisting of hospitalized individuals.

title:
  Mathematical analysis of the role of hospitalization/isolation in controlling the spread of Zika fever

abstract:
  The Zika virus is transmitted to humans primarily through Aedes mosquitoes and through sexual contact. It is documented that the virus can be transmitted to newborn babies from their mothers. We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. The total populations of both humans and mosquitoes are assumed to be constant. Our models consist of a system of eight differential equations describing the human and vector populations during the different stages of the disease. We have included the hospitalization/isolation class in our model to see the effect of the controlling strategy. We determine the expression for the basic reproductive number R(0) in terms of horizontal as well as vertical disease transmission rates. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R(0) < 1. It is also shown that when R(0) > 1, there exists a unique endemic equilibrium. We showed that the endemic equilibrium point is globally asymptotically stable when it exists. We were able to prove this result in a reduced model. Furthermore, we conducted an uncertainty and sensitivity analysis to recognize the impact of crucial model parameters on R(0). The uncertainty analysis yields an estimated value of the basic reproductive number R(0) = 1.54. Assuming infection prevalence in the population under constant control, optimal control theory is used to devise an optimal hospitalization/isolation control strategy for the model. The impact of isolation on the number of infected individuals and the accumulated cost is assessed and compared with the constant control case.


id: cord-294764-v28wbrqp
title: Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses
author: Deval, Jerome
date: 2017-04-15
url: https://doi.org/10.1016/j.virusres.2016.12.018
doi: 10.1016/j.virusres.2016.12.018
abstract:
  Noroviruses belong to the Caliciviridae family of single-stranded positive-sense RNA viruses. The genus Norovirus includes seven genogroups (designated GI-GVII), of which GI, GII and GIV infect humans. Human noroviruses are responsible for widespread outbreaks of acute gastroenteritis and represent one of the most common causes of foodborne illness. No vaccine or antiviral treatment options are available for norovirus infection. The RNA-dependent RNA polymerase (RdRp) of noroviruses is a key enzyme responsible for transcription and replication of the viral genome. Here, we review the progress made in understanding the structures and functions of norovirus RdRp and its use as a target for small molecule inhibitors. Crystal structures of the RdRp at different stages of substrate interaction have been determined, which shed light on its multi-step catalytic cycle. The in vitro assays and in vivo animal models that have been developed to identify and characterize inhibitors of norovirus RdRp are also summarized, followed by an update on the current antiviral research targeting different regions of norovirus RdRp. In the future, structure-based drug design and rational optimization of known nucleoside and non-nucleoside inhibitors of norovirus RdRp may pave the way towards the next generation of direct-acting antivirals.


id: cord-295099-ghc85pf5
title: Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies
author: Sun, Zehua
date: 2018-01-02
txt: ./txt/cord-295099-ghc85pf5.txt
cache: ./cache/cord-295099-ghc85pf5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2017.10.011
doi: 10.1016/j.virusres.2017.10.011
summary:
  Antibody responses to neutralize human immunodeficiency virus-1 (HIV-1) are mediated by direct binding to viral spikes, which are trimers composed of glycoproteins gp120 and gp41 (Pincus et al., 2017a; Pincus et al., 2017b; Blair et al., 2007; Morris et al., 2000; Micoli et al., 2000; Pegu et al., 2017; Haynes and Mascola, 2017; Liao et al., 2004; Brodine et al., 2003; Ward and Wilson, 2017; Debnath et al., 1994; Moore et al., 1993) . M43 and m44 are HIV-1 cross-reactive human monoclonal antibodies isolated from a recombinant phage display library by competitive antigen panning (Zhang et al., 2012; Zhang et al., 2008; Zhang et al., 2006; Zhang et al., 2004a; Zhang et al., 2004b) . HIV-1 specific antibodies isolated by display techniques are less potent than those isolated by micro neutralization or single B cell sorting and cloning. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries

abstract:
  HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization. The isolation and characterization of large panels of potent human broadly neutralizing antibodies has revealed new insights into the principles of antibody-mediated neutralization of HIV. In this paper, we review the current effective techniques in broadly neutralizing antibody isolation.


id: cord-295187-konm26x5
title: Full-length genome analysis of canine coronavirus type I
author: Decaro, Nicola
date: 2015-12-02
txt: ./txt/cord-295187-konm26x5.txt
cache: ./cache/cord-295187-konm26x5.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170215300228
doi: 10.1016/j.virusres.2015.07.018
summary:
  However, two distinct features were observed in the CCoV-I genome: (i) the presence of an additional ORF between the spike (S) protein gene and ORF3a; (ii) the diversity of the S protein, which is more closely related to that of feline coronavirus type I and presents a furin cleavage site. Canine coronavirus (CCoV) is usually responsible for mild enteritis in young dogs Buonavoglia, 2008, 2011) , although fatal disease has been associated to a pantropic variant of the virus (Decaro et al., , 2010a Marinaro et al., 2010; Zicola et al., 2012; Ntafis et al., 2012) . Alignment of complete genome sequences of CCoV-I strain 23/03 and reference alphacoronaviruses showed the closest genetic relatedness with CCoV-IIa isolates (83.82-84.98% nt identity), followed by TGEV (82.81%) and . Molecular characterization of a canine coronavirus NA/09 strain detected in a dog''s organs

abstract:
  Canine coronavirus types I (CCoV-I) and II (CCoV-II) are usually responsible for mild enteritis in dogs. While the CCoV-II genome has been completely sequenced, to date there are no complete genomic sequence data available publicly for CCoV-I. Thus, the aim of the present study was to analyze the full-length genome of a CCoV-I prototype strain that had been recovered from a dog with diarrhea in Italy. CCoV-I strain 23/03 has a genome of 30,000 nucleotides, excluding the 3′ poly(A) tail, displaying the typical Alphacoronavirus-1 organization and the highest genetic relatedness to CCoV-II. However, two distinct features were observed in the CCoV-I genome: (i) the presence of an additional ORF between the spike (S) protein gene and ORF3a; (ii) the diversity of the S protein, which is more closely related to that of feline coronavirus type I and presents a furin cleavage site. The present study may contribute to a better understanding of the Alphacoronavirus-1 evolutionary pattern and may be paradigmatic of how coronaviruses evolve through gene losses, acquisition and exchanges among different members.


id: cord-299904-i5c6nf18
author: Cornelissen, E.
date: 2009-04-07
txt: ./txt/cord-299904-i5c6nf18.txt
cache: ./cache/cord-299904-i5c6nf18.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2009.03.017
doi: 10.1016/j.virusres.2009.03.017
summary:
  authors: Cornelissen, E.; Dewerchin, H.L.; Van Hamme, E.; Nauwynck, H.J. title: Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP Feline infectious peritonitis virus-infected monocytes internalize viral membrane-bound proteins upon antibody addition

title:
  Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells

abstract:
  Cats infected with virulent feline coronavirus which causes feline infectious peritonitis (FIP) usually succumb to disease despite high antibody concentrations. One of the mechanisms that can help resolving infection is antibody-dependent, complement-mediated lysis (ADCML) of infected cells. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. The objective of this study was to determine the sensitivity of FIP-virus (FIPV) infected cells towards ADCML and to examine the role of the accessory proteins 3abc and 7ab in this process. ADCML assays, using FIPV strain 79-1146 and its deletion mutant strain Δ3abc/Δ7ab, were performed on: (i) CrFK cells that show surface-expressed viral antigens, (ii) monocytes without surface-expressed viral proteins due to retention and (iii) monocytes with surface-expressed viral proteins since the antibody-mediated internalization of these proteins was blocked. As expected, no ADCML was detected of the monocytes without surface-expressed viral antigens. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. These experiments proof that FIPV can employ another immune evasion strategy against ADCML (besides preventing surface expression): the inhibition of complement-mediated lysis. This new evasion strategy is not attributed to the group-specific proteins since lysis of cells infected with FIPV Δ3abc/Δ7ab was not detected.


id: cord-300883-rws11uel
title: Positive natural selection in the evolution of human metapneumovirus attachment glycoprotein
author: Padhi, Abinash
date: 2007-10-10
txt: ./txt/cord-300883-rws11uel.txt
cache: ./cache/cord-300883-rws11uel.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170207003279
doi: 10.1016/j.virusres.2007.08.014
summary:
  We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV. Although comparative genome mapping analyses suggested that this virus has structural and functional similarities with HRSV (Kahn, 2006) , recent studies reported that the attachment (G) glycoprotein of these paramimyxoviruses exhibit extensive nucleotide and amino acid variation, with most differences located in the extracellular domain (Peret et al., 2004; Kahn, 2006) . Here we used Yang et al''s (2000) ML codon substitution models to test whether there was evidence at the nucleotide sequence level that a subset of amino acid sites in G-protein of hMPV sequences that represent each subgroup has been under positive selection.

abstract:
  Human metapneumovirus (hMPV), a newly discovered virus of the family Paramyxoviridae, has been associated with upper and lower respiratory tract infections in different age groups in many countries. The putative attachment (G) glycoprotein of this virus was previously reported to have shown more extensive nucleotide and deduced amino acid sequence polymorphism than any other genomic regions of this virus, leading to four sub-lineages. Using a maximum likelihood-based codon substitution model of sequence evolution, here we report that sequences of extracellular domain of 8 amino acid sites in lineage 1a, and 3 amino acid sites each in lineage 1b, 2a, and 2b have a higher rate of nonsynonymous substitutions (d(N)) than the synonymous substitutions (d(S)) with a posterior probability above 0.95, thus suggesting the evidence of adaptive evolution driven by Darwinian selection. Although it is unclear whether these amino acid adaptations are driven by differential immune pressure or some other factors, identification of these positively selected amino acid sites would help in better screening using epitope mapping technology to identify and localize the sites that can be recognized by the immune system. We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV.


id: cord-301151-f6vya3qh
title: Co-infection with respiratory pathogens among COVID-2019 cases
author: Zhu, Xiaojuan
date: 2020-05-11
txt: ./txt/cord-301151-f6vya3qh.txt
cache: ./cache/cord-301151-f6vya3qh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2020.198005
doi: 10.1016/j.virusres.2020.198005
summary:
  In this study, the clinical features of COVID-19 patients were analyzed, then 39 respiratory pathogens in their throat swab were detected by specific real-time RT-PCR. 257 patients were diagnosed with the SARS-CoV-2 infection and their clinical severity was classified according to National Health Commission of the People''s Republic of China revised criteria for diagnosis and treatment of novel coronavirus infection pneumonia (trial version fifth, revised version). Below 15 years of age, a total of 11 (4.3 %) were diagnosed with the SARS-CoV-2 infection and there were no case in severe/critical category. In our study, 94.2 % of COVID-19 patients could be co-infected with one or more other pathogens, including 9 viruses, 11 bacteria and 4 fungi. Along with the course of disease, both the rates and pathogen species of co-infection among COVID-19 patients were decreased significantly, which may due to the treatment X.

abstract:
  Accumulating evidence shows that microbial co-infection increases the risk of disease severity in humans. There have been few studies about SARS-CoV-2 co-infection with other pathogens. In this retrospective study, 257 laboratory-confirmed COVID-19 patients in Jiangsu Province were enrolled from January 22 to February 2, 2020. They were re-confirmed by real-time RT-PCR and tested for 39 respiratory pathogens. In total, 24 respiratory pathogens were found among the patients, and 242 (94.2 %) patients were co-infected with one or more pathogens. Bacterial co-infections were dominant in all COVID-19 patients, Streptococcus pneumoniae was the most common, followed by Klebsiella pneumoniae and Haemophilus influenzae. The highest and lowest rates of co-infections were found in patients aged 15–44 and below 15, respectively. Most co-infections occurred within 1–4 days of onset of COVID-19 disease. In addition, the proportion of viral co-infections, fungal co-infections and bacterial-fungal co-infections were the highest severe COVID-19 cases. These results will provide a helpful reference for diagnosis and clinical treatment of COVID-19 patients.


id: cord-301301-ilsenpus
author: Mihalov-Kovács, Eszter
date: 2017-03-15
txt: ./txt/cord-301301-ilsenpus.txt
cache: ./cache/cord-301301-ilsenpus.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170216305731
doi: 10.1016/j.virusres.2016.12.005
summary:
  Interestingly, this strain possessed unique genetic signatures (including a longer ORF1b/ORF2 overlap and a longer 3′UTR) and it was divergent in both ORF1b and ORF2 from all other canine astroviruses, with the highest nucleotide sequence identity (68% and 63%, respectively) to a mink astrovirus, thus suggesting a possible event of interspecies transmission. A total of 63 samples obtained from 50 animals were tested for AstV by using a pan-astrovirus specific primer set (Chu et al., 2008) as described elsewhere (Mihalov-Kovács et al., 2014) and 37 (from 33 dogs) were randomly selected for viral metagenomics. The complete ORF1b was 1530 nt long in all canine AstVs, except the partially sequenced strain, HUN/2012/8, where a 770 nt long portion was determined. In addition, upon sequence comparison and phylogenetic analysis, strain HUN/2012/8 differed markedly from other canine AstVs concerning the partial ORF1b and the full-length ORF2 (Table 3) .

title:
  Genome analysis of canine astroviruses reveals genetic heterogeneity and suggests possible inter-species transmission

abstract:
  Canine astrovirus RNA was detected in the stools of 17/63 (26.9%) samples, using either a broadly reactive consensus RT-PCR for astroviruses or random RT-PCR coupled with massive deep sequencing. The complete or nearly complete genome sequence of five canine astroviruses was reconstructed that allowed mapping the genome organization and to investigate the genetic diversity of these viruses. The genome was about 6.6 kb in length and contained three open reading frames (ORFs) flanked by a 5′ UTR, and a 3′ UTR plus a poly-A tail. ORF1a and ORF1b overlapped by 43 nucleotides while the ORF2 overlapped by 8 nucleotides with the 3′ end of ORF1b. Upon genome comparison, four strains (HUN/2012/2, HUN/2012/6, HUN/2012/115, and HUN/2012/135) were more related genetically to each other and to UK canine astroviruses (88–96% nt identity), whilst strain HUN/2012/126 was more divergent (75–76% nt identity). In the ORF1b and ORF2, strains HUN/2012/2, HUN/2012/6, and HUN/2012/135 were related genetically to other canine astroviruses identified formerly in Europe and China, whereas strain HUN/2012/126 was related genetically to a divergent canine astrovirus strain, ITA/2010/Zoid. For one canine astrovirus, HUN/2012/8, only a 3.2 kb portion of the genome, at the 3′ end, could be determined. Interestingly, this strain possessed unique genetic signatures (including a longer ORF1b/ORF2 overlap and a longer 3′UTR) and it was divergent in both ORF1b and ORF2 from all other canine astroviruses, with the highest nucleotide sequence identity (68% and 63%, respectively) to a mink astrovirus, thus suggesting a possible event of interspecies transmission. The genetic heterogeneity of canine astroviruses may pose a challenge for the diagnostics and for future prophylaxis strategies.


id: cord-302083-9q1i20o6
author: Jung, Kwonil
date: 2020-06-02
txt: ./txt/cord-302083-9q1i20o6.txt
cache: ./cache/cord-302083-9q1i20o6.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170220301209
doi: 10.1016/j.virusres.2020.198045
summary:
  PEDV infection of neonatal pigs causes fecal virus shedding (alongside frequent detection of PEDV RNA in the nasal cavity), acute viremia, severe atrophic enteritis (mainly jejunum and ileum), and increased pro-inflammatory and innate immune responses. Detection of viremia where viral RNA in serum ranged from 4.5-8.6 log10 genomic equivalents (GE)/ml was identified in gnotobiotic neonatal (5/5; 100%), or conventional 9-dayold nursing (16/16; 100%) and 26-day-old weaned pigs (11/20; 55%) infected with a US non-S INDEL PEDV strain at PID 1-5 (Jung et al., 2015a; Jung et al., 2014) . Cross protective immune responses in nursing piglets infected with a US spike-insertion deletion porcine epidemic diarrhea virus strain and challenged with an original US PEDV strain Goblet cell depletion in small intestinal villous and crypt epithelium of conventional nursing and weaned pigs infected with porcine epidemic diarrhea virus.

title:
  Porcine epidemic diarrhea virus (PEDV): An update on etiology, transmission, pathogenesis, and prevention and control

abstract:
  Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration and high mortality in neonatal piglets. Two different genogroups of PEDV, S INDEL [PEDV variant containing multiple deletions and insertions in the S1 subunit of the spike (S) protein, G1b] and non-S INDEL (G2b) strains were detected during the diarrheal disease outbreak in US swine in 2013-2014. Similar viruses are also circulating globally. Continuous improvement and update of biosecurity and vaccine strains and protocols are still needed to control and prevent PEDV infections worldwide. Although the non-S INDEL PEDV was highly virulent and the S INDEL PEDV caused milder disease, the latter has the capacity to cause illness in a high number of piglets on farms with low biosecurity and herd immunity. The main PEDV transmission route is fecal–oral, but airborne transmission via the fecal–nasal route may play a role in pig-to-pig and farm-to-farm spread. PEDV infection of neonatal pigs causes fecal virus shedding (alongside frequent detection of PEDV RNA in the nasal cavity), acute viremia, severe atrophic enteritis (mainly jejunum and ileum), and increased pro-inflammatory and innate immune responses. PEDV-specific IgA effector and memory B cells in orally primed sows play a critical role in sow lactogenic immunity and passive protection of piglets. This review focuses on the etiology, transmission, pathogenesis, and prevention and control of PEDV infection.


id: cord-303111-iv4lzpev
title: Reprint of: Coronavirus reverse genetic systems: Infectious clones and replicons()
author: Almazán, Fernando
date: 2014-12-19
txt: ./txt/cord-303111-iv4lzpev.txt
cache: ./cache/cord-303111-iv4lzpev.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170214003827
doi: 10.1016/j.virusres.2014.09.006
summary:
  Until recently, the study of CoV genetics was broadly restricted to the analysis of temperature-sensitive (ts) mutants Baric, 1992, 1994; Lai and Cavanagh, 1997; Schaad and Baric, 1994; Stalcup et al., 1998) , defective RNA templates which depend on replicase proteins provided in trans by a helper virus (Izeta et al., 1999; Narayanan and Makino, 2001; Repass and Makino, 1998; Williams et al., 1999) , and recombinant viruses generated by targeted recombination (Masters, 1999; Masters and Rottier, 2005 reverse genetic system devised for CoVs at a time when it was not clear whether the construction of full-length infectious cDNA clones would ever be technically feasible. These reverse genetic systems have been established using non-traditional approaches, which are based on the use of targeted recombination, BACs, in vitro ligation of CoV cDNA fragments, and vaccinia virus as a vector for the propagation of CoV genomic cDNAs. The availability of CoV full-length infectious clones and recombinant viruses expressing reporter genes constitute important tools for the study of CoV replication and transcription mechanisms, virus-host interaction and pathogenesis, and also for the rapid and rational development and testing of genetically defined vaccines.

abstract:
  Coronaviruses (CoVs) infect humans and many animal species, and are associated with respiratory, enteric, hepatic, and central nervous system diseases. The large size of the CoV genome and the instability of some CoV replicase gene sequences during its propagation in bacteria, represent serious obstacles for the development of reverse genetic systems similar to those used for smaller positive sense RNA viruses. To overcome these limitations, several alternatives to more conventional plasmid-based approaches have been established in the last 13 years. In this report, we briefly review and discuss the different reverse genetic systems developed for CoVs, paying special attention to the severe acute respiratory syndrome CoV (SARS-CoV).


id: cord-304137-vxqkztio
title: A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent
author: Bueno, Carlos A.
date: 2009-01-20
txt: ./txt/cord-304137-vxqkztio.txt
cache: ./cache/cord-304137-vxqkztio.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170208004504
doi: 10.1016/j.virusres.2008.12.013
summary:
  We have reported that meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., exerts an antiviral action on the development of herpetic stromal keratitis (HSK) in mice by causing a significant decrease in the viral load in the eye of Herpes simplex virus type 1 (HSV-1) infected animals, as well as in the incidence and severity of lesions due to a virus-induced immunopathological reaction (Pifarré et al., 2002) . We have found that CDM is able to block HSV-1 induced activation of NF-B by inhibiting its translocation to the nucleus of infected human conjunctival cells (NHC), and postulated that CDM would be able to abolish murine HSK by controlling viral spread and the associated immunopathology as well (Barquero et al., 2006) . The aim of the present study was to determine whether CDM displays an antiviral activity in infected corneal cells, the target of HSV-1 multiplication in vivo, as well as its effect on the translocation of NF-B to the nucleus.

abstract:
  Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., prevents the development of herpetic stromal keratitis (HSK) in mice by diminishing the viral load in the eye and the severity of lesions caused by a virus-induced immunopathological reaction. The tetranortriterpenoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA purification, displays anti-herpetic activity and impedes nuclear factor κB (NF-κB) activation in HSV-1 infected conjunctival cells. To extend our understanding about CDM biological properties, we investigated its anti-HSV-1 activity as well as the effect on NF-κB activation and cytokine secretion induced by viral (HSV-1) and no-viral (LPS) stimuli, in corneal cells and macrophages. CDM exerted a potent anti-HSV-1 effect on corneal cells and inhibited NF-κB translocation to the nucleus, leading to a decrease in IL-6 production. Besides, CDM seemed to modulate IL-6 and TNF-α responses in macrophages, whether they were infected with HSV-1 or stimulated with LPS. However, CDM did not affect NF-κB activation in these cells, suggesting that an alternative NF-κB cell signaling pathway would be involved in the modulation of cytokine production. We conclude that, in addition to its antiviral effect, CDM would be acting as an immunomodulating compound which would be responsible for the improvement of murine HSK already reported.


id: cord-304424-048xo7jn
title: A decade of RNA virus metagenomics is (not) enough
author: Greninger, Alexander L.
date: 2018-01-15
url: https://www.ncbi.nlm.nih.gov/pubmed/29055712/
doi: 10.1016/j.virusres.2017.10.014
abstract:
  It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found.


id: cord-309205-l8vjtrjq
author: Shirato, Kazuya
date: 2018-08-15
txt: ./txt/cord-309205-l8vjtrjq.txt
cache: ./cache/cord-309205-l8vjtrjq.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2018.06.010
doi: 10.1016/j.virusres.2018.06.010
summary:
  The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). Despite some concerns relating to the precise identity of the FCoV strains 79-1683 and 79-1146, to be discussed later, but lacking better options to address this critical issue in the pathogenesis of FIP, we continued in the present study with investigating the contributions of the amino acids in the spike S2 domain differing between the prototypic strains to the distinguishing macrophage tropism of these viruses. There are eleven amino acid differences in the C-terminal domain of the S proteins of FIPV 79-1146 and FECV 79-1683 to which we mapped these viruses'' differential ability to infect macrophages (Fig. 1c) .

title:
  Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein

abstract:
  The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). In view of the later identified diagnostic difference in this very part of the S protein of serotype I FCoV pathotypes, the present study aimed to further define the contribution of the earlier observed ten amino acids difference to the serotype II virus phenotype in macrophages. Using targeted RNA recombination as a reverse genetics system we introduced the mutations singly and in combinations into the S gene and evaluated their effects on the infection characteristics of the mutant viruses in macrophages. While some of the single mutations had a significant effect, none of them fully reverted the infection phenotype. Only by combining five specific mutations the infections mediated by the FIPV and FECV spike proteins could be fully blocked or potentiated, respectively. Hence, the differential macrophage infection phenotype is caused by the cooperative effect of five mutations, which occur in five functionally different domains of the spike fusion subunit S2. The significance of these observations will be discussed, taking into account also some questions related to the identity of the virus strains used.


id: cord-309428-qkjjxr6p
author: Li, Liwei
date: 2015-01-02
url: https://www.sciencedirect.com/science/article/pii/S0168170214003402
doi: 10.1016/j.virusres.2014.08.012
title:
  Host miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by upregulating type I interferons

abstract:
  MicroRNAs (miRNAs) play important roles in viral infections, especially by modulating the expression of cellular factors essential to viral replication or the host innate immune response to infection. To identify host miRNAs important to controlling porcine reproductive and respiratory syndrome virus (PRRSV) infection, we screened 15 miRNAs that were previously implicated in innate immunity or antiviral functions. Over-expression of the miR-26 family strongly inhibited PRRSV replication in vitro, as shown by virus titer assays, Western blotting, and qRT-PCR assays. MiR-26a inhibited the replication of both type 1 and type 2 PRRSV strains. Mutating the seed region of miR-26 restored viral titers. Luciferase reporters showed that miR-26a does not target the PRRSV genome directly but instead affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. These results demonstrate the important role of miR-26a in modulating PRRSV infection and also support the possibility of using host miR-26a to achieve RNAi-mediated antiviral therapeutic strategies.


id: cord-311628-ep795pil
title: A novel delivery platform based on Bacteriophage MS2 virus-like particles
author: Fu, Yu
date: 2016-01-04
txt: ./txt/cord-311628-ep795pil.txt
cache: ./cache/cord-311628-ep795pil.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S016817021530054X
doi: 10.1016/j.virusres.2015.08.022
summary:
  Our objective here is to review the novel delivery platform based on Bacteriophage MS2 virus-like particles (VLPs), including introduction to their structure, their potential as a delivery platform, and their expected use in medicine and other fields. A series of research findings showed that an MS2 VLP-based vaccine can effectively induce innate and cognate immune responses and can be used as a specific preventive intervention in some diseases, such as foot-and-mouth disease (Bittle et al., 1982; Dong et al., 2015; Van Lierop et al., 1992; Wong et al., 2000) , prostate cancer (Li et al., 2014) , and illnesses caused by human papilloma virus (HPV) (Tumban et al., 2012) . These particles offer an effective and convenient way to package RNAs, DNAs, epitope peptides, and drugs into bacteriophage capsids, forming different kinds of VLPs. MS2 VLPs can not only deliver various kinds of agents with a good safety profile and strong immunogenicity but also ensure tissue-specific targeting, which is determined by the species of the virus.

abstract:
  Our objective here is to review the novel delivery platform based on Bacteriophage MS2 virus-like particles (VLPs), including introduction to their structure, their potential as a delivery platform, and their expected use in medicine and other fields. Bacteriophage MS2 VLPs are nanoparticles devoid of viral genetic material and can self-assemble from the coat protein into an icosahedral capsid. As a novel delivery platform, they possess numerous features that make them suitable and attractive for targeted delivery of RNAs or DNAs, epitope peptides, and drugs within the protein capsid. In short, as a novel delivery platform, MS2 VLPs are suitable for delivery of targeted agents and hold promise for use in diagnostics, vaccines, and therapeutic modalities.


id: cord-312489-ywep0c08
title: Decreased neutralizing antigenicity in IBV S1 protein expressed from mammalian cells
author: Andoh, Kiyohiko
date: 2015-10-02
txt: ./txt/cord-312489-ywep0c08.txt
cache: ./cache/cord-312489-ywep0c08.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170215002841
doi: 10.1016/j.virusres.2015.06.019
summary:
  We evaluated the antigenicity of recombinant infectious bronchitis virus (IBV) S1 protein expressed in mammalian cells. Native S1 ELISA detected similar titers in the sera of animals immunized with recombinant S1 protein compared to those in sera of chickens immunized with inactivated virus (Fig. 6b ) (Control experiments (data not shown) demonstrated that mock and unvaccinated control groups did not differ from each other in VN and ELISA tests of anti-S1 activity.) These results indicated that while recombinant S1 protein retained antigenicity (the ability to induce antibodies against S1 protein), the resulting antibodies was decreased its neutralizing activity, in contrast to those induced by inactivated virus. The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus

abstract:
  We evaluated the antigenicity of recombinant infectious bronchitis virus (IBV) S1 protein expressed in mammalian cells. Recombinant S1 was expressed as a secreted protein fused with a trimerization motif peptide, then purified using Ni Sepharose. The purified protein was analyzed by Western blotting, mixed with oil adjuvant, and administered to 29-day-old specific-pathogen-free chickens. Six weeks after immunization, anti-IBV neutralizing titer and anti-S1 ELISA titer were determined; immunized chickens then were inoculated with IBV via the trachea and ciliary activity was observed. Results showed that the recombinant S1 protein was highly glycosylated, and the neutralizing antigenicity of recombinant S1 protein was lower than that of inactivated virus. However, anti-S1 ELISA indicated that the recombinant S1 protein induced antibodies against S1. These results suggest that the recombinant S1 may retain non-neutralizing epitopes but have unnatural glycosylation pattern and conformation, resulting in lacking neutralizing conformational epitopes. In conclusion, the neutralizing antigenicity of recombinant S1 protein expressed from mammalian cells was decreased, and was not sufficient to induce neutralizing antibodies.


id: cord-312848-vbadg8ki
author: Jeong, Jae-Ho
date: 2004-08-26
txt: ./txt/cord-312848-vbadg8ki.txt
cache: ./cache/cord-312848-vbadg8ki.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170204002850
doi: 10.1016/j.virusres.2004.07.003
summary:
  In the present study, we analyzed the S glycoprotein gene to characterize 10 winter dysentery (WD) coronavirus strains circulated in Korea during 2002–2003 and compared the nucleotide (nt) and deduced amino acid (aa) sequences with the other known BCoV. The phylogenetic analysis of the entire S glycoprotein gene revealed that the aa sequences of all Korean WD strains were more homologous to each other and were very closely related to respiratory bovine coronavirus (RBCV) strain OK and enteric bovine coronavirus (EBCV) strain LY-138, but were distinct from the other known BCoVs. Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, all Korean WD strains clustered with the respiratory strain OK, BCQ3994 and the enteric strain LY-138, while the Canadian BCQ calf diarrhea and WD strains, and the American RBCV LSU, French EBCV F15 and avirulent VACC, L9, and Mebus strains clustered on a separate major branch.

title:
  Molecular analysis of S gene of spike glycoprotein of winter dysentery bovine coronavirus circulated in Korea during 2002–2003

abstract:
  Since the molecular analysis of spike (S) glycoprotein gene of bovine coronavirus (BCoV) has been conducted and compared mainly among American and Canadian isolates and/or strains, it is unclear whether BCoV circulated in the other countries are distinctive in genetic characteristics. In the present study, we analyzed the S glycoprotein gene to characterize 10 winter dysentery (WD) coronavirus strains circulated in Korea during 2002–2003 and compared the nucleotide (nt) and deduced amino acid (aa) sequences with the other known BCoV. The phylogenetic analysis of the entire S glycoprotein gene revealed that the aa sequences of all Korean WD strains were more homologous to each other and were very closely related to respiratory bovine coronavirus (RBCV) strain OK and enteric bovine coronavirus (EBCV) strain LY-138, but were distinct from the other known BCoVs. Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, all Korean WD strains clustered with the respiratory strain OK, BCQ3994 and the enteric strain LY-138, while the Canadian BCQ calf diarrhea and WD strains, and the American RBCV LSU, French EBCV F15 and avirulent VACC, L9, and Mebus strains clustered on a separate major branch. These data suggest that the WD strains circulated in Korea had a genetic property of both RBCV and EBCV and were significantly distinct from the ancestral enteric strain.


id: cord-314415-yr0uxok2
author: Guo, Zijing
date: 2018-08-15
txt: ./txt/cord-314415-yr0uxok2.txt
cache: ./cache/cord-314415-yr0uxok2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2018.07.015
doi: 10.1016/j.virusres.2018.07.015
summary:
  In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The result showed that Bo-Circo-like virus CH is clustered into a independent branch with seven reported strains of proposed family Kirkoviridae and eight CRESS-DNA virus strains recently submitted to GenBank database; Bo-Circo-like virus CH is more closely related to Po-Circo-like virus and shows significant genetic differences with viruses in the families Circoviridae, Nanoviridae, Geminiviridae Genomoviridae, Bacilladnaviridae and Smacoviridae (Fig. 3) . The sequence alignments included strain Bo-Circo-like virus CH in this study, representative members of the Circoviridae, Geminiviridae, Nanoviridae, Genomoviridae, Bacilladnaviridae and Smacoviridae families, the proposed new genera of krikoviruses, and still unassigned novel CRESS-DNA viruses with the best BLASTp matchs in GenBank database. The sequence alignments included five Bo-Circo-like virus strains detected in this study and seven reported strains of the proposed family Kirkoviridae.

title:
  Identification and genomic characterization of a novel CRESS DNA virus from a calf with severe hemorrhagic enteritis in China

abstract:
  In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The virus, named Bo-Circo-like virus CH, has a circular genome with 3909 nucleotides (nt). Six putative open reading frames (ORFs) were identified, including Rep, capsid (Cap) and four proteins of unknown function. Both the genome size and the number as well as the organization of encoded ORFs, Bo-Circo-like virus CH is most closely related to Po-Circo-like virus 21 detected in pig faeces. A preliminary survey using specific primers for the Rep region showed that 5.3% (4/75) of diarrheic samples were positive for Bo-Circo-like virus, and all 42 healthy samples were negative. In conclusion, our results indicate that Bo-Circo-like virus CH may represent a new virus in bovine. Further investigation is needed to determine the relationship between the virus infection and diarrhea.


id: cord-317061-0bx704ao
author: Wu, Andong
date: 2015-10-02
url: https://api.elsevier.com/content/article/pii/S0168170215002178
doi: 10.1016/j.virusres.2015.05.018
title:
  Prediction and biochemical analysis of putative cleavage sites of the 3C-like protease of Middle East respiratory syndrome coronavirus

abstract:
  Coronavirus 3C-like protease (3CLpro) is responsible for the cleavage of coronaviral polyprotein 1a/1ab (pp1a/1ab) to produce the mature non-structural proteins (nsps) of nsp4–16. The nsp5 of the newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as 3CLpro and its canonical cleavage sites (between nsps) were predicted based on sequence alignment, but the cleavability of these cleavage sites remains to be experimentally confirmed and putative non-canonical cleavage sites (inside one nsp) within the pp1a/1ab awaits further analysis. Here, we proposed a method for predicting coronaviral 3CLpro cleavage sites which balances the prediction accuracy and false positive outcomes. By applying this method to MERS-CoV, the 11 canonical cleavage sites were readily identified and verified by the biochemical assays. The Michaelis constant of the canonical cleavage sites of MERS-CoV showed that the substrate specificity of MERS-CoV 3CLpro is relatively conserved. Interestingly, nine putative non-canonical cleavage sites were predicted and three of them could be cleaved by MERS-CoV nsp5. These results pave the way for identification and functional characterization of new nsp products of coronaviruses.


id: cord-318319-efqf5e1i
author: Yamasaki, Yukitaka
date: 2020-07-03
txt: ./txt/cord-318319-efqf5e1i.txt
cache: ./cache/cord-318319-efqf5e1i.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2020.198089
doi: 10.1016/j.virusres.2020.198089
summary:
  The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. Many patients with coronavirus infection disease 2019(COVID-19) are subclinical, and it has been reported that people are J o u r n a l P r e -p r o o f contagious even when asymptomatic [1, 2] , which means preventing the spread of SARS-CoV-2 is challenging [3] . Risk factors of severe pneumonia include age, comorbidities, smoking, reduced lymphocyte count, elevated ferritin levels, and elevated C-reactive protein (CRP) levels [4] [5] [6] [7] [8] [9] . In addition, we examined whether ciclesonide could prevent the development of severe COVID-19 among patients with these predictors. Moreover, the lymphocyte count after ciclesonide therapy in the non-severe pneumonia group was significantly higher (p=0.0156) compared to before treatment (mean 6.14 days, SD 2.17) (Figure 3b ).

title:
  The peripheral lymphocyte count as a predictor of severe COVID-19 and the effect of treatment with ciclesonide

abstract:
  We investigated whether reduced lymphocyte count, could predict the development of severe COVID-19. We also examined whether ciclesonide could prevent the development of severe COVID-19 among patients with the predictors. This was a retrospective cohort study. Of the 30 included patients, 12, 14, and 4 were allocated to severe pneumonia, non-severe pneumonia, and non-pneumonia groups, respectively. The group of the low level of lymphocyte counts of the sixth day after onset was significantly intubated approximately three days later. The incidence of the severe pneumoniae requiring intubation are significantly lower in the patients treated with ciclesonide than without it (11.18 % vs 83.33%, p = 0.0033). The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. 0156) than before. The lymphocyte count could be used to identify patients that may develop severe COVID-19. Treatment with ciclesonide may prevent the development of severe COVID-19.


id: cord-320331-wtxja5i9
author: Cabbab, Iris Louise N.
date: 2020-10-08
url: https://doi.org/10.1016/j.virusres.2020.198190
doi: 10.1016/j.virusres.2020.198190
title:
  Anti-Inflammatory Drugs and the Renin-Angiotensin-Aldosterone System: Current Knowledge and Potential Effects on Early SARS-CoV-2 Infection

abstract:
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 19 (COVID-19), and is genetically related to the 2003 SARS and Middle East respiratory syndrome (MERS-CoV) coronaviruses. Recent studies have reported that similar to SARS-CoV, this strain expresses a spike protein (S) with a receptor binding domain (RBD) that binds to angiotensin-converting enzyme 2 (ACE2) – an enzyme expressed mostly in the endothelium, kidneys, heart, gastrointestinal tract and lungs – to facilitate viral entry and intracellular replication. Incidentally, the renin-angiotensin-aldosterone system (RAAS) is integral to physiologic control of both ACE and ACE2 expression, and is an essential system utilized by SARS-CoV-2, albeit with varying schools of thought on how it can affect viral entry. In this paper, we will review current knowledge on the RAAS and how it can be affected by non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid use at the organ and cellular levels. We will then discuss the relevance of these interactions on organ-specific ACE2 expression, and provide scientific insights on how this mechanism can potentially affect SARS-CoV-2 infection in the early phases of disease. From the standpoint of other known viruses, we will then aim to discuss the potential uses or restrictions of these drugs in viral infection, and provide an update on relevant studies about COVID-19.


id: cord-325973-e3rxr6oq
author: Navarro, Ryan
date: 2017-08-15
txt: ./txt/cord-325973-e3rxr6oq.txt
cache: ./cache/cord-325973-e3rxr6oq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28847699/
doi: 10.1016/j.virusres.2017.08.008
summary:
  Although the current CPV vaccines, derived from the original CPV-2 strains, or CPV-2b strains, have been shown to confer protective immunity against CPV disease, and post-vaccination reactions have rarely been encountered in immunized dogs, the emergence of new genetic and antigenic variants underscores the importance of constant http://dx.doi.org/10.1016/j.virusres.2017.08.008 Received 16 May 2017; Received in revised form 10 July 2017; Accepted 21 August 2017 monitoring of evolution patterns of CPV strains circulating in dogs throughout the world (Decaro and Buonavoglia, 2012; Miranda and Thompson, 2016) . Although the prevalence and genetic diversity of CPV and CCoV in dogs have been extensively studied in different parts of the world including nearby Latin American countries, there are no reports on these important canine viruses from the Caribbean region so far. We report here the detection and molecular characterization of CPV and CCoV strains in dogs with diarrhea on the Caribbean island of St. Kitts (KNA).

title:
  Molecular characterization of canine parvovirus and canine enteric coronavirus in diarrheic dogs on the island of St. Kitts: First report from the Caribbean region

abstract:
  Although canine parvovirus (CPV) and canine enteric coronavirus (CCoV) are important enteric pathogens of dogs and have been studied extensively in different parts of the world, there are no reports on these viruses from the Caribbean region. During 2015–2016, a total of 104 diarrheic fecal samples were collected from puppies and adult dogs, with or without hemorrhagic gastroenteritis, on the Caribbean island of St. Kitts (KNA). By PCR, 25 (24%, n = 104) samples tested positive for CPV. Based on analysis of the complete deduced VP2 amino acid sequences, 20 of the KNA CPV strains were assigned to new CPV-2a (also designated as CPV-2a-297A). On the other hand, the VP2 genes of the remaining 5 strains were partially characterized, or could not be sequenced. New CPV-2a was the predominant CPV variant in St. Kitts, contrasting the molecular epidemiology of CPV variants reported in most studies from nearby North and South American countries. By RT-PCR, CCoVs were detected in 5 samples (4.8%, n = 104). Based on analysis of partial M-protein gene, the KNA CCoV strains were assigned to CCoV-I genotype, and were closely related to CCoV-I strains from Brazil. To our knowledge, this is the first report on detection and genetic diversity of CPV and CCoV in dogs from the Caribbean region, and underscores the importance of similar studies in the other Caribbean islands.


id: cord-326320-flfrdrbi
author: Choudhary, Shalki
date: 2020-08-29
txt: ./txt/cord-326320-flfrdrbi.txt
cache: ./cache/cord-326320-flfrdrbi.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170220310534?v=s5
doi: 10.1016/j.virusres.2020.198146
summary:
  title: Scaffold morphing of arbidol (umifenovir) in search of multi-targeting therapy halting the interaction of SARS-CoV-2 with ACE2 and other proteases involved in COVID-19 The multi-targeting potential of generated analogues was explored against various targets involved in the pathogenesis of COVID-19 including SARS-CoV-2 SP, ACE2, furin, TMPRSS2 (in viral attachment) and 3CLPro (in viral replication). A cutoff value of 3 was used for the screening of compounds based on synthetic possibility and topranked molecules were submitted to structure-guided drug binding analysis such as molecular docking studies. All these molecules were docked against SARS-CoV-2 SP-ACE2 complex, furin, TMPRSS2 and main protease (3CLPro) and the binding affinity of their docked complexes was also calculated in terms of MM-GBSA score. J o u r n a l P r e -p r o o f 44 A combination of scaffold morphing and a structure-based drug designing approach was successfully utilized to identify putative multi-targeting analogues of arbidol against COVID-19.

title:
  Scaffold morphing of arbidol (umifenovir) in search of multi-targeting therapy halting the interaction of SARS-CoV-2 with ACE2 and other proteases involved in COVID-19

abstract:
  The rapid emergence of a novel coronavirus, SARS-coronavirus 2 (SARS-CoV-2), originated from Wuhan, China, imposed a global health emergency. Angiotensin-converting enzyme 2 (ACE2) receptor serves as an entry point for this deadly virus while the proteases like furin, transmembrane protease serine 2 (TMPRSS2) and 3 chymotrypsin-like protease (3CLpro) are involved in the further processing and replication of SARS-CoV-2. The interaction of SP with ACE2 and these proteases results in the SARS-CoV-2 invasion and fast epidemic spread. The small molecular inhibitors are reported to limit the interaction of SP with ACE2 and other proteases. Arbidol, a membrane fusion inhibitor approved for influenza virus is currently undergoing clinical trials against COVID-19. In this context, we report some analogues of arbidol designed by scaffold morphing and structure-based designing approaches with a superior therapeutic profile. The representative compounds A_BR4, A_BR9, A_BR18, A_BR22 and A_BR28 restricted the interaction of SARS-CoV-2 SP with ACE2 and host proteases furin and TMPRSS2. For 3CLPro, Compounds A_BR5, A_BR6, A_BR9 and A_BR18 exhibited high binding affinity, docking score and key residue interactions. Overall, A_BR18 and A_BR28 demonstrated multi-targeting potential against all the targets. Among these top-scoring molecules A_BR9, A_BR18, A_BR22 and A_BR28 were predicted to confer favorable ADME properties.


id: cord-326349-59566vqe
author: Ding, Li
date: 2013-12-26
txt: ./txt/cord-326349-59566vqe.txt
cache: ./cache/cord-326349-59566vqe.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170213003286
doi: 10.1016/j.virusres.2013.09.036
summary:
  In addition, TGEV infection of the cells synchronized in various stages of cell cycle showed that viral genomic RNA and subgenomic RNA, and virus titer were higher in the cells released from S-phaseor G2/M phase-synchronized cells than that in the cells released from the G0/G1 phase-synchronized or asynchronous cells after 18 h p.i. Taken together, our data suggested that TGEV infection induced S and G2/M phase arrest in host cells, which might provide a favorable condition for viral replication. To further determine the roles of p53 in TGEV-induced cell cycle arrest, we investigated the effects of PFT-␣, a specific inhibitor of p53 that does not affect the mRNA levels of TGEV genes (Huang et al., 2013) , on the cell cycle profiles and the expression of p21, cdks and cyclins in TGEV-infected PK-15 and ST cells. As shown in Fig. 6B , pre-incubation of PK-15 and ST cells with PFT-␣ attenuated cell cycle arrest at S and G2/M phase induced by TGEV infection.

title:
  Transmissible gastroenteritis virus infection induces cell cycle arrest at S and G2/M phases via p53-dependent pathway

abstract:
  p53 signaling pathway plays an important role in the regulation of cell cycle. Our previous studies have demonstrated that TGEV infection induces the activation of p53 signaling pathway. In this study we investigated the effects of TGEV infection on the cell cycle of host cells and the roles of p53 activation in this process. The results showed that TGEV infection induced cell cycle arrest at S and G2/M phases in both asynchronous and synchronized PK-15 and ST cells, while UV-inactivated TGEV lost the ability of induction of cell cycle arrest. TGEV infection promoted p21 accumulation, down-regulated cell cycle-regulatory proteins cyclins B1, cdc2, cdk2 and PCNA. Further studies showed that inhibition of p53 signaling could attenuate the TGEV-induced S- and G2/M-phase arrest by reversing the expression of p21 and corresponding cyclin/cdk. In addition, TGEV infection of the cells synchronized in various stages of cell cycle showed that viral genomic RNA and subgenomic RNA, and virus titer were higher in the cells released from S-phase- or G2/M phase-synchronized cells than that in the cells released from the G0/G1 phase-synchronized or asynchronous cells after 18 h p.i. Taken together, our data suggested that TGEV infection induced S and G2/M phase arrest in host cells, which might provide a favorable condition for viral replication.


id: cord-327682-i3uim0zi
title: Molecular detection and typing of human picornaviruses
author: Santti, Juhana
date: 1999-08-25
txt: ./txt/cord-327682-i3uim0zi.txt
cache: ./cache/cord-327682-i3uim0zi.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170299000362
doi: 10.1016/s0168-1702(99)00036-2
summary:
  It has been shown in a number of studies that virtually all the enterovirus serotypes and most of the HRV isolates can be detected using these primer sequences (Hyypiä et , 1989; Horsnell et al., 1995; Pulli et al., 1995; Arola et al., 1996; Huttunen et al., 1996; Pitkäranta et al., 1997; Hyypiä et al., 1998; Oberste et al., 1998) The authors became convinced of the usefulness of this technique during a recent outbreak of aseptic meningitis in Finland. Partial sequence analysis of virtually all enterovirus serotypes has shown that they belong to these four clusters (Pulli et al., 1995; Huttunen et al., 1996) and that the VP4/VP2 region sequence can be used for molecular typing of clinical isolates (Arola et al., 1996) . In hepatitis A virus infections, the molecular epidemiology has been investigated by many reseach groups and an extensive analysis of partial sequences from different geographic locations has been used to establish a useful database for further studies (Robertson et al., 1992) .

abstract:
  Picornaviruses include several important clinical pathogens which cause diseases varying from common cold to poliomyelitis and hepatitis. Introduction of RT-PCR methods for the detection of these viruses has significantly facilitated the diagnosis of picornavirus infections and elucidated their etiological role in clinical illnesses. Partial sequence analysis of the genomes has been used for typing of the viruses and in studies of molecular epidemiology of picornaviruses. These molecular approaches are likely to become the most predominant techniques for the diagnosis and epidemiological analysis, particularly in the enterovirus infections.


id: cord-329183-s0zrvn9o
author: Graham, Robert I.
date: 2008-04-10
txt: ./txt/cord-329183-s0zrvn9o.txt
cache: ./cache/cord-329183-s0zrvn9o.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18405997/
doi: 10.1016/j.virusres.2008.02.005
summary:
  title: Sequence analysis of a reovirus isolated from the winter moth Operophtera brumata (Lepidoptera: Geometridae) and its parasitoid wasp Phobocampe tempestiva (Hymenoptera: Ichneumonidae)() When the protein encoded by ObRV Seg-10 was expressed (by inserting the open reading frame into a baculovirus expression vector) no ''occlusion bodies'' were observed in the recombinant baculovirus infected insect cell cultures. Seg-1 of ObRV is 4170 nt in length (Table 1) , with a single large ORF between nt 33 and 4109 (stop codon TGA), coding for a predicted protein of 1358 aa (155.7 kDa), which is identified as VP1. Although the lack of sequence information from this genus (particularly the RdRp), makes it difficult to make further comparisons, the data presented here, together with the detection of an eleventh genome segment in female wasps (Graham et al., 2006) , suggest that ObRV represents a new member (a new species) within the genus Idnoreovirus, which contains other non-occluded insect reoviruses.

title:
  Sequence analysis of a reovirus isolated from the winter moth Operophtera brumata (Lepidoptera: Geometridae) and its parasitoid wasp Phobocampe tempestiva (Hymenoptera: Ichneumonidae)()

abstract:
  A reovirus was isolated from Operophtera brumata (ObRV) and its parasitoid wasp Phobocampe tempestiva. Each of the 10 dsRNA genome segments of ObRV was sequenced and shown to contain a single open reading frame (ORF). Conserved motifs ([+ve] 5′-AAATAAA … (G)/(T)AGGTT-3′) were found at the termini of each segment, with the exception of Seg-6 and Seg-8, where the 5′ termini were 5′-AACAAA…-3′. The putative proteins encoded by each segment were compared with those of other members of the family Reoviridae. Phylogenetic comparisons to published sequences for the RNA-dependent RNA polymerase genes from other reoviruses indicated that ObRV is most closely related to members of the genus Cypovirus. However, unlike the cypoviruses, ObRV has a double-layered capsid structure. When the protein encoded by ObRV Seg-10 was expressed (by inserting the open reading frame into a baculovirus expression vector) no ‘occlusion bodies’ were observed in the recombinant baculovirus infected insect cell cultures. This suggests that unlike the cypoviruses, Seg-10 of ObRV does not contain a polyhedrin gene. Further phylogenetic comparisons also identified relationships between Seg-2 and Seg-10 of ObRV, and genes of Diadromus pulchellus Idnoreovirus 1 (DpIRV1), suggesting that ObRV represents a new species from the genus Idnoreovirus.


id: cord-330260-xuw31zfn
title: Identification of Taiwan and China-like recombinant avian infectious bronchitis viruses in Taiwan
author: Chen, Hui-Wen
date: 2009-01-20
txt: ./txt/cord-330260-xuw31zfn.txt
cache: ./cache/cord-330260-xuw31zfn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19100792/
doi: 10.1016/j.virusres.2008.11.012
summary:
  All of the recombinants showed chimeric IBV genome arrangements originated from Taiwan and China-like parental strains. Phylogenetic analyses were performed based on the nucleotide sequence alignment using each ORF from the S to N genes among eight Taiwan and reference strains (Fig. 1) . Phylogenetic analysis of partial S1 and N gene sequences of infectious bronchitis virus isolates from Italy revealed genetic diversity and recombination Recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism A novel variant of avian infectious bronchitis virus resulting from recombination among three different strains Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus Genetic diversity of avian infectious bronchitis coronavirus strains isolated in China between Genetic grouping for the isolates of avian infectious bronchitis virus in Taiwan

abstract:
  Infectious bronchitis virus (IBV) infections in poultry cause great economic losses to the poultry industry worldwide. The emergence of viral variants complicates disease control. The IBV strains in Taiwan were clustered into two groups, Taiwan group I and Taiwan group II, based on the S1 gene. A variant was previously identified and showed a distinct S1 gene homology with other local strains. This study investigated the 3′ 7.3 kb genome of eight Taiwan strains isolated from 1992 to 2007. The genes of interest were directly sequenced. Sequence analyses were performed to detect any recombination event among IBVs. The results demonstrated that all of the examined viruses maintained the typical IBV genome organization as 5′-S-3a-3b-E-M-5a-5b-N-UTR-3′. In the phylogenetic analyses, various genes from one strain were clustered into separate groups. Moreover, frequent recombination events were identified in the Simplot analyses among the Taiwan and China CK/CH/LDL/97I-type strains. Putative crossover sites were located in the S1, S2, 3b, M genes and the intergenic region between the M and 5a genes. All of the recombinants showed chimeric IBV genome arrangements originated from Taiwan and China-like parental strains. Field IBVs in Taiwan undergo genetic recombination and evolution.


id: cord-330508-uilejxmi
author: van den Hoogen, Bernadette
date: 2020-07-28
txt: ./txt/cord-330508-uilejxmi.txt
cache: ./cache/cord-330508-uilejxmi.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170220309400?v=s5
doi: 10.1016/j.virusres.2020.198094
summary:
  While molecular details of the innate immune response are well characterized, this research field is now being revolutionized with the recognition that cell metabolism has a major impact on the antiviral and inflammatory responses to virus infections. While molecular details of the innate immune response are well characterized, this research field is now being revolutionized with the recognition that cell metabolism has a major impact on the antiviral and inflammatory responses to virus infections. A detailed understanding of the role of metabolic regulation with respect to antiviral and inflammatory responses, together with knowledge of the strategies used by viruses to exploit immunometabolic pathways, will ultimately change our understanding and treatment of pathogenic viral diseases. A detailed understanding of the role of metabolic regulation with respect to antiviral and inflammatory responses, together with knowledge of the strategies used by viruses to exploit immunometabolic pathways, will ultimately change our understanding and treatment of pathogenic viral diseases.

title:
  Immunometabolism pathways as the basis for innovative anti-viral strategies (INITIATE): A Marie Sklodowska-Curie innovative training network

abstract:
  The past century has witnessed major advances in the control of many infectious diseases, yet outbreaks and epidemics caused by (re-) emerging RNA viruses continue to pose a global threat to human health. As illustrated by the global COVID19 pandemic, high healthcare costs, economic disruption and loss of productivity reinforce the unmet medical need to develop new antiviral strategies to combat not only the current pandemic but also future viral outbreaks. Pivotal for effective anti-viral defense is the innate immune system, a first line host response that senses and responds to virus infection. While molecular details of the innate immune response are well characterized, this research field is now being revolutionized with the recognition that cell metabolism has a major impact on the antiviral and inflammatory responses to virus infections. A detailed understanding of the role of metabolic regulation with respect to antiviral and inflammatory responses, together with knowledge of the strategies used by viruses to exploit immunometabolic pathways, will ultimately change our understanding and treatment of pathogenic viral diseases. INITIATE is a Marie Sklodowska-Curie Actions Innovative Training Network (MSCA-ITN), with the goal to train 15 early stage PhD researchers (ESRs) to become experts in antiviral immunometabolism (https://initiate-itn.eu/). To this end, INITIATE brings together a highly complementary international team of academic and corporate leaders from 7 European countries, with outstanding track records in the historically distinct research fields of virology, immunology and metabolism. The ESRs of INITIATE are trained in these interdisciplinary research fields through individual investigator-driven research projects, specialized scientific training events, workshops on academia-industry interactions, outreach & communication. INITIATE will deliver a new generation of creative and entrepreneurial researchers who will be able to face the inevitable future challenges in combating viral diseases.


id: cord-332075-gxmae2rs
author: Wang, Jianzhong
date: 2015-05-04
txt: ./txt/cord-332075-gxmae2rs.txt
cache: ./cache/cord-332075-gxmae2rs.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170215001409
doi: 10.1016/j.virusres.2015.04.006
summary:
  title: Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds. To evaluate whether this genotype VII isolate could be used as a vaccine vector for geese we generated a recombinant virus rmNA-VP3 expressing VP3 protein of GPV after modifying the polybasic F cleavage site of NA-1 to the dibasic motif of LaSota.

title:
  Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings

abstract:
  Newcastle disease virus (NDV) and Goose parvovirus (GPV) are considered to be two of the most important and widespread viruses infecting geese. In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. Expression of the VP3 protein in rmNA-VP3 infected cells was detected by immunofluorescence and Western blot assay. The genetic stability was examined by serially passaging 10 times in 10-day-old embryonated SPF chicken eggs. Goslings were inoculated with rmNA-VP3 showed no apparent signs of disease and developed a strong GPV and NDV neutralizing antibodies response. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds.


id: cord-332317-wrztpeb8
author: Zhang, Xin
date: 2015-03-16
url: https://www.ncbi.nlm.nih.gov/pubmed/25533531/
doi: 10.1016/j.virusres.2014.12.013
title:
  Identification of the interaction between vimentin and nucleocapsid protein of transmissible gastroenteritis virus

abstract:
  Nucleocapsid (N) protein of transmissible gastroenteritis virus (TGEV) packages viral RNA genome to form a ribonucleoprotein complex. In addition to its function as a structural protein, N protein is involved in cell apoptosis or cell-cycle regulation. N protein possibly interacts with host factors to modulate cellular functions. To identify cellular proteins that interacted with N protein of TGEV, methods of GST pull-down and Co-IP were utilized to precipitate cellular proteins of swine testicular (ST). Bound cellular proteins were resolved by SDS-PAGE. Analysis of interacting proteins by mass spectrometry allowed identification of 15 cellular protein bands representative of 12 cellular proteins including vimentin that bound to N protein. Furthermore, the function of vimentin cytoskeleton in ST cells during TGEV infection was examined. Vimentin cytoskeleton was required for virus replication. The present study thus provides protein-related information about interaction of TGEV N protein with host cell that should be useful for understanding host cell response to coronavirus pathogenesis infection and the underlying mechanism of coronavirus replication.


id: cord-333180-xevie6tm
title: How do viruses control mitochondria-mediated apoptosis?
author: Neumann, Simon
date: 2015-11-02
url: https://doi.org/10.1016/j.virusres.2015.02.026
doi: 10.1016/j.virusres.2015.02.026
abstract:
  There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can “sense” viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This “sacrifice” of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host.


id: cord-335706-lopcb77c
author: Tan, Feifei
date: 2011-03-24
url: https://api.elsevier.com/content/article/pii/S0168170211001018
doi: 10.1016/j.virusres.2011.03.011
title:
  Identification of non-essential regions in nucleocapsid protein of porcine reproductive and respiratory syndrome virus for replication in cell culture

abstract:
  Nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) plays a central role in virus replication. In this study, serial N- and C-terminal truncations of N protein were performed in the context of type 2 PRRSV infectious cDNA clone, and our results revealed that a stretch of inter-genotypic variable N terminal residues aa 5–13 ((5)NGKQQKKK(13)K) and the last four inter-genotypic variable aa residues ((120)SPS(123)A) at the C terminus of N protein were dispensable for type 2 PRRSV infectivity. All the recovered deletion mutant viruses had spontaneous mutations in the N coding region, including substitution, deletion and insertion. We re-engineered the additional internal deletion with or without the original C-terminal deletion back into wild-type APRRS and found that the internal domain spanning the inter-genotypic variable residues 39–42 ((39)KGP(42)G) and conserved residues 48–52 ((48)KNPE(52)K), respectively, were dispensable for type 2 PRRSV viability. These results demonstrated that N protein contains non-essential regions for virus viability in cell culture. Such dispensable regions could be utilized as insertion site for foreign tag expression and the rescued viruses could be the candidates for marker vaccine.


id: cord-338602-6n309bnp
author: Gadotti, Ana Carolina
date: 2020-09-23
txt: ./txt/cord-338602-6n309bnp.txt
cache: ./cache/cord-338602-6n309bnp.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170220310789?v=s5
doi: 10.1016/j.virusres.2020.198171
summary:
  title: IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. A reasonable hypothesis is that (i) pro-inflammatory innate immunity and (ii) anti-inflammatory system are related to disease severity or death once IL-6, IL-8, and IL10 are closely described as prognostic factors in patients diagnosed with COVID-19 1, 3, 7 . Previous studies have not reported the association between IFN-γ and death, even evaluating the COVID-19-reactive CD69+ expressing IFN-γ producing CD8+ T in 25 patients with severe and moderate disease 22 . Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan Levels of cytokines from patients with moderate and severe COVID-19 infection according to the outcome (data in the median with IQR)

title:
  IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection

abstract:
  BACKGROUND: Innate and adaptive immune responses have been evaluated in infected patients with COVID-19. The severity of the disease has been supposed to be associated with some profile not reported with other bacterial and viral pneumonia. We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. METHODS: A prospective cohort with moderate and severe cases of COVID-19 infection from June to July 2020. Blood samples from patients were collected regularly to evaluate IFN-γ, TNF-α, IL-4, IL-6, and IL-10. Clinical, laboratory, radiological data, and outcomes were recorded. The outcome variable was in-hospital death, survival, mechanical ventilation, and admission at the intensive care unit. Data are presented in median and interquartile range [IQR]. RESULTS: We evaluated the Th1 and Th2 responses according to evolution, distinguishing possible predictive markers. The IFN-γ median of 323 pg/mL [IQR 166-570] was found in patients who died and 208 pg/mL [IQR 155-392] in the survival group (p = 0.017). IFN-γ was also higher in the early stages of the disease (394 pg/mL [IQR 229-575] against 162 pg/mL [IQR 117-259], p < 0.001). IL-4 that was increased in late-stage (182 pg/mL [IQR 162-199] against 131 pg/mL [IQR 124-152], p < 0.001) but not associated with mortality. Also, death was also related to male gender (relative risk = 1.5 [95% confidence interval = 1.1-2.0]). CONCLUSION: Our results suggest that the activation of the host immune response between Th1 or Th2 in COVID-19 infection may be related to the final result between discharge or death. This implies an attempt to control cytokines, such as IFN-γ, with combined therapies for clinical treatment.


id: cord-344084-z4t2wkgk
title: Beyond HIV infection: neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases
author: Ellwanger, Joel Henrique
date: 2020-05-30
txt: ./txt/cord-344084-z4t2wkgk.txt
cache: ./cache/cord-344084-z4t2wkgk.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170220302938
doi: 10.1016/j.virusres.2020.198040
summary:
  The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. In agreement with studies showing that CCR5Δ32 homozygous genotype is a risk factor for symptomatic WNV infection in humans, Ccr5-/-WNV-infected mice showed a reduced capacity of viral control, increased disease severity, impaired leukocyte trafficking towards the brain, and high mortality rates than Ccr5 wild-type mice. In conclusion, although tissue analysis and evidence obtained in vitro suggest that the CCR5 is potentially involved in the pathogenesis of HPV, most studies point to a lack of involvement of CCR5Δ32 in susceptibility to HPV infection or HPV-associated diseases.

abstract:
  The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human C-C chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in “CCR5 research” are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.


id: cord-345999-iiw4cs8p
author: Khare, Prashant
date: 2020-09-24
txt: ./txt/cord-345999-iiw4cs8p.txt
cache: ./cache/cord-345999-iiw4cs8p.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170220310765
doi: 10.1016/j.virusres.2020.198169
summary:
  Since it is a newly emerging viral disease and obviously there is a lack of anti-SARS-CoV-2 therapeutic agents, it is urgently required to develop an effective anti-SARS-CoV-2-agent.Through recent advancements in computational biology and biological assays, several natural compounds and their derivatives have been reported to confirm their target specific antiviral potential against Middle East respiratory syndrome coronavirus (MERS-CoV) or Severe Acute Respiratory Syndrome(SARS-CoV).These targets including an important host cell receptor, i.e., angiotensin-converting enzyme ACE2 and several viral proteins e.g. spike glycoprotein (S) containing S1 and S2 domains, SARS CoV Chymotrypsin-like cysteine protease (3CL(pro)), papain-like cysteine protease (PL(pro)), helicases and RNA-dependent RNA polymerase (RdRp). For the management J o u r n a l P r e -p r o o f of COVID-19 infection, various molecular targets playing important role in the SARS-CoV-2 life cycle including host cell receptor-Angiotensin-converting enzyme ACE2 (PDB ID 3D0G) and viral proteins such as S protein (containing S1 and S2 domains) (PDB ID 6XM0); various cysteine proteases such as papain-like cysteine protease (PL pro ) (PDB ID 6WX4) or Chymotrypsin like nprotease (3CL pro ) (PDB ID 1P9U), helicases and RNA-dependent RNA polymerase (RdRp) (PDB ID 6M71) could be evaluated .

title:
  Current approaches for target-specific drug discovery using natural compounds against SARS-CoV-2 infection

abstract:
  The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) recently caused a pandemic outbreak called coronavirus disease 2019 (COVID-19). This disease has initially been reported in China and also now it is expeditiously spreading around the globe directly among individuals through coughing and sneezing. Since it is a newly emerging viral disease and obviously there is a lack of anti-SARS-CoV-2 therapeutic agents, it is urgently required to develop an effective anti-SARS-CoV-2-agent.Through recent advancements in computational biology and biological assays, several natural compounds and their derivatives have been reported to confirm their target specific antiviral potential against Middle East respiratory syndrome coronavirus (MERS-CoV) or Severe Acute Respiratory Syndrome(SARS-CoV).These targets including an important host cell receptor, i.e., angiotensin-converting enzyme ACE2 and several viral proteins e.g. spike glycoprotein (S) containing S1 and S2 domains, SARS CoV Chymotrypsin-like cysteine protease (3CL(pro)), papain-like cysteine protease (PL(pro)), helicases and RNA-dependent RNA polymerase (RdRp). Due to physical, chemical, and some genetic similarities of SARS CoV-2 with SARS−COV and MERS−COV, repurposing various anti-SARS−COV or anti-MERS−COV natural therapeutic agents could be helpful for the development of anti−COVID-19 herbal medicine. Here we have summarized various drug targets in SARS−COV and MERS−COV using several natural products and their derivatives, which could guide researchers to design and develop a safe and cost-effective anti-SARS−COV-2 drugs.


id: cord-346104-18x8u2oe
title: Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus)
author: Black, Wendy
date: 2019-01-02
txt: ./txt/cord-346104-18x8u2oe.txt
cache: ./cache/cord-346104-18x8u2oe.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170218303678
doi: 10.1016/j.virusres.2018.10.016
summary:
  Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). To determine whether the observed viral particles are herpesviruses, tissues collected from the two NV black bears B1 and B2 were examined by nested PCR using panherpesvirus primers (Pozo et al., 2016 ) and herpesvirus consensus primers (VanDevanter et al., 1996) . To determine how common this UrHV-1 like virus is in black bear population, various tissues from 15 bears collected from Nevada, California, and Oregon were analyzed by this hybrid nested PCR with panherpesvirus primers in primary reaction and UrHV-1specific primers in the secondary reactions. Positive amplification with UrHV-1 specific primers was observed in total DNA of white blood cells (WBC) from two black bears from Nevada and one from Oregon.

abstract:
  Herpesvirus infection was investigated in black bears (Ursus americanus) with neurological signs and brain lesions of nonsuppurative encephalitis of unknown cause. Visible cytopathic effects (CPE) could only be observed on days 3–5 post-infection in HrT-18G cell line inoculated with bear tissue extracts. The observed CPE in HrT-18G cells included syncytia, intranuclear inclusions, and cell detachments seen in herpesvirus infection in vitro. Herpesvirus-like particles were observed in viral culture supernatant under the electron microscope, however, capsids ranging from 60 nm to 100 nm in size were often observed in viral cultures within the first two passages of propagation. Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). DNA sequencing of the amplicon revealed that the detected herpesvirus has 94–95% identity to Ursid gammaherpesvirus 1 (UrHV-1) DNA sequences of DPOL. Phylogenetic analysis of DPOL sequences indicates that black bear herpesviruses and UrHV-1 are closely related and have small distances to members of Rhadinovirus. Interestingly, black bear herpesvirus infections were also found in bears without neurological signs. The DPOL DNA sequence of black bear herpesviruses detected in neurological bears were similar to the those detected in the non-neurological bears. However, the gB DNA sequence detected from the neurological bear is different from non-neurological bear and has only 64.5%–70% identity to each other. It is possible that at least two different types of gammaherpesviruses are present in the U. americanus population or several gammaherpesviruses exist in ursine species.


id: cord-346264-hnwgzt6v
title: Porcine sapoviruses: Pathogenesis, epidemiology, genetic diversity, and diagnosis
author: Nagai, Makoto
date: 2020-05-26
txt: ./txt/cord-346264-hnwgzt6v.txt
cache: ./cache/cord-346264-hnwgzt6v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32470356/
doi: 10.1016/j.virusres.2020.198025
summary:
  Although GIII Cowden strain replicated in the villous epithelial cells and caused intestinal lesions in the proximal small intestines (mainly in duodenal and less in jejunum), leading to mild to severe diarrhea, in the orally inoculated neonatal gnotobiotic pigs, the significance of porcine SaVs in different ages of pigs with diarrhea in the field is still undetermined. The first porcine sapovirus (SaV), the Cowden strain was discovered by electron microscopy in the intestinal contents of a 27-day-old diarrheic nursing pig in the United State in 1980 (Saif et al., 1980 . In this review, we will summarize current knowledge on the pathogenesis of GIII Cowden strain, the epidemiology and genetic diversity of porcine SaVs, and the diagnosis of SaV infection in pigs. It may also explain why porcine SaV Cowden strain did not replicate in other organs when piglets were inoculated intravenously (IV) with the virus (Guo et al., 2001) .

abstract:
  The first porcine Sapovirus (SaV) Cowden strain was discovered in 1980. To date, eight genogroups (GIII, V-IX) and three genogroups (GIII, GV, and GVI) of porcine SaVs have been detected from domestic pigs worldwide and wild boars in Japan, respectively based on the capsid sequences. Although GIII Cowden strain replicated in the villous epithelial cells and caused intestinal lesions in the proximal small intestines (mainly in duodenal and less in jejunum), leading to mild to severe diarrhea, in the orally inoculated neonatal gnotobiotic pigs, the significance of porcine SaVs in different ages of pigs with diarrhea in the field is still undetermined. This is due to two reasons: 1) similar prevalence of porcine SaVs was detected in diarrheic and non-diarrheic pigs; and 2) co-infection of porcine SaVs with other enteric pathogens is common in pigs. Diagnosis of porcine SaV infection is mainly based on the detection of viral nucleic acids using reverse transcription (RT)-PCR and sequencing. Much is unknown about these genetically diverse viruses to understand their role in pig health and to evaluate whether vaccines are needed to prevent SaV infection.


id: cord-347270-x05tfkgx
author: Lu, Shuai
date: 2017-06-02
url: https://www.sciencedirect.com/science/article/pii/S0168170217302332
doi: 10.1016/j.virusres.2017.05.006
title:
  Discovery of a novel canine respiratory coronavirus support genetic recombination among betacoronavirus1

abstract:
  Although canine respiratory coronavirus (CRCoV) is an important respiratory pathogen that is prevalent in many countries, only one complete genome sequence of CRCoV (South Korea strain K37) has been obtained to date. Genome-wide analyses and recombination have rarely been conducted, as small numbers of samples and limited genomic characterization have previously prevented further analyses. Herein, we report a unique CRCoV strain, denoted strain BJ232, derived from a CRCoV-positive dog with a mild respiratory infection. Phylogenetic analysis based on complete genome of all available coronaviruses consistently show that CRCoV BJ232 is most closely related to human coronavirus OC43 (HCoV-OC43) and BCoV, forming a separate clade that split off early from other Betacoronavirus 1. Based on the phylogenetic and SimPlot analysis we propose that CRCoV-K37 was derived from genetic recombination between CRCoV-BJ232 and BCoV. In detail, spike (S) gene of CRCoV-K37 clustered with CRCoV-BJ232. However orf1ab, membrane (M) and nucleocapsid (N) genes were more related to Bovine coronavirus (BCoV) than CRCoV-B232. Molecular epidemic analysis confirmed the prevalence of CRCoV-BJ232 lineage around the world for a long time. Recombinant events among Betacoronavirus 1 may have implications for CRCoV transmissibility. All these findings provide further information regarding the origin of CRCoV.


id: cord-347924-w06ho8sn
title: Computational prediction and identification of dengue virus-specific CD4(+) T-cell epitopes
author: Wen, Jin-Sheng
date: 2007-12-03
txt: ./txt/cord-347924-w06ho8sn.txt
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extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0168170207003735
doi: 10.1016/j.virusres.2007.10.010
summary:
  In this study, we tried to identify dengue virus-specific CD4(+) T-cell epitopes, which can induce PBMC (peripheral blood mononuclear cells) isolated from DF convalescent patients (dengue virus type 1 infection) to secrete IFN-γ. Currently, many studies suggested that dengue-specific T-cell immune response are hypothesized to play an important role in the immunopathogenesis of DHF during a secondary DEN virus infection, and induction of immunopathology by T lymphocytes may occur by various mechanisms, including cell-mediated cytotoxicity and/or cytokine production (Miskovsky et al., 1994; Vergelli et al., 1997) . In the present study, a combination of bioinformatics tools (epitope-prediction programs RANKpep) and in vitro assays (enzyme-linked immunospot assay (ELISPOT) and intracel-lular cytokine staining assay (ICS)) was used to screen and select antigen sequences as potential DEN-specific CD4 + T-cell epitopes, then the selected sequences are tested for biological function by their activation of T cells of DEN infected populations.

abstract:
  In this study, we tried to identify dengue virus-specific CD4(+) T-cell epitopes, which can induce PBMC (peripheral blood mononuclear cells) isolated from DF convalescent patients (dengue virus type 1 infection) to secrete IFN-γ. PBMC of DF convalescent patients were stimulated in vitro with dengue virus-derived peptides, which were prepared based on the prediction of dengue virus-specific CD4(+) T-cell epitopes by using RANKpep online software. Subsequently, the frequency of IFN-γ producing T cells and percentage of IFN-γ(+) CD4(+) T cells were measured by using ELISPOT assay and ICS assay (intracellular cytokine straining), respectively. The positive response of PBMC by ELISPOT showed that the numbers of SFC (spots forming cells) ranged from 50 to 310 SFC/1 × 10(6) PBMC. The positive response of PBMC by ICS assay showed that the percentage of IFN-γ(+) CD4(+) T cells ranged from 0.03 to 0.27%. As a result, C(45-57) (KLVMAFIAFLRFL), E(396-408) (SSIGKMFEATARG), NS3(23-35) (YRILQRGLLGRSQ), and NS3(141-155) (NREGKIVGLYGNGVV) were identified as dengue virus-specific CD4(+) T-cell epitopes.


id: cord-351766-ik89889i
title: Melatonin potentials against viral infections including COVID-19: current evidence and new findings
author: Juybari, Kobra Bahrampour
date: 2020-08-05
txt: ./txt/cord-351766-ik89889i.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2020.198108
doi: 10.1016/j.virusres.2020.198108
summary:
  It is well-known that melatonin as an anti-oxidative and anti-inflammatory agent counters acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by viral and bacterial infections. In addition to mentioned viral infectious diseases, melatonin has been shown to play therapeutic roles in infection induced by Ebola virus. The Ebola virus increases blood coagulation, weakens the immune system, and mediates noticeable inflammatory responses leading to the oxidative stress-induced organ and cellular damages. (2020) Beside oxidative cell injury induced by SARS-CoV-2, serum inflammatory markers such as D-dimers, C-reactive protein, and ferritin, neutrophil count in a complete blood count (CBC), and inflammatory cytokines, and chemokines increase in severe COVID-19 patients (Merad and Martin, 2020a; Ruan et al., 2020) . Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic Influenza A (H7N9) infection, a hint for COVID-19 treatment Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice

abstract:
  Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.


