Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
20
05
2020
accepted:
27
10
2020
revised:
23
12
2020
pubmed:
12
12
2020
medline:
29
1
2021
entrez:
11
12
2020
Statut:
epublish
Résumé
Modified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence and break vaccinal protection. Since the introduction of the first vaccine in the 1970s, Marek's disease virus overcame the vaccine barrier by the acquisition of numerous genomic mutations. However, the evolutionary adaptations in the herpesvirus genome responsible for the vaccine breaks have remained elusive. Here, we demonstrate that point mutations in the multifunctional meq gene acquired during evolution can significantly alter virulence. Defined mutations found in highly virulent strains also allowed the virus to overcome innate cellular responses and vaccinal protection. Concomitantly, the adaptations in meq enhanced virus shedding into the environment, likely providing a selective advantage for the virus. Our study provides the first experimental evidence that few point mutations in a single herpesviral gene result in drastically increased virulence, enhanced shedding, and escape from vaccinal protection.
Identifiants
pubmed: 33306739
doi: 10.1371/journal.ppat.1009104
pii: PPATHOGENS-D-20-01067
pmc: PMC7758048
doi:
Substances chimiques
Eco-Q protein, Gallid herpesvirus 2
0
Marek Disease Vaccines
0
Oncogene Proteins, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009104Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Biotechniques. 2006 Feb;40(2):191-7
pubmed: 16526409
Viruses. 2019 Mar 16;11(3):
pubmed: 30884829
Bull World Health Organ. 2008 Feb;86(2):140-6
pubmed: 18297169
Virus Genes. 2011 Aug;43(1):66-71
pubmed: 21503681
J Biomed Biotechnol. 2012;2012:472537
pubmed: 22496607
Virology. 2004 Oct 10;328(1):142-50
pubmed: 15380365
J Vet Med Sci. 2000 Mar;62(3):287-92
pubmed: 10770601
J Virol. 2000 Dec;74(23):11088-98
pubmed: 11070004
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Transbound Emerg Dis. 2020 Jan;67(1):98-107
pubmed: 31411371
Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1687-92
pubmed: 16446447
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):12878-12886
pubmed: 30559199
Vet J. 2005 Sep;170(2):175-83
pubmed: 16129338
Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13879-84
pubmed: 15356338
BMC Syst Biol. 2012 Sep 14;6:123
pubmed: 22979947
Virus Genes. 2000;21(1-2):51-64
pubmed: 11022789
J Exp Med. 2011 Mar 14;208(3):605-15
pubmed: 21383055
Avian Dis. 1972 Apr;16(1):108-25
pubmed: 4337307
Vet Microbiol. 2004 Sep 8;102(3-4):147-67
pubmed: 15327791
Sci Rep. 2018 Jan 9;8(1):209
pubmed: 29317752
Avian Dis. 2014 Dec;58(4):550-7
pubmed: 25618999
Avian Pathol. 2005 Apr;34(2):75-90
pubmed: 16191686
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Evol Appl. 2017 Sep 03;10(10):1091-1101
pubmed: 29151863
Vet Res. 2014 Apr 03;45:36
pubmed: 24694064
PLoS Pathog. 2019 Sep 20;15(9):e1007999
pubmed: 31539404
Vet J. 2015 Sep;205(3):339-48
pubmed: 26067852
Microorganisms. 2019 Nov 20;7(12):
pubmed: 31757008
PLoS One. 2016 Sep 23;11(9):e0162180
pubmed: 27662574
Virus Res. 2009 Jun;142(1-2):57-67
pubmed: 19189855
Virol J. 2010 Nov 26;7:348
pubmed: 21110861
Expert Rev Vaccines. 2005 Feb;4(1):77-88
pubmed: 15757475
Avian Pathol. 2012;41(3):267-75
pubmed: 22702454
J Virol. 2006 Feb;80(3):1160-6
pubmed: 16414993
J Gen Virol. 2019 Jul;100(7):1132-1139
pubmed: 31184569
Nat Microbiol. 2019 Nov;4(11):2025
pubmed: 31576018
J Exp Med. 2006 May 15;203(5):1307-17
pubmed: 16651385
Avian Dis. 2013 Jun;57(2 Suppl):440-7
pubmed: 23901759
Avian Dis. 2012 Jun;56(2):328-40
pubmed: 22856190
PLoS Pathog. 2010 Aug 26;6(8):e1001073
pubmed: 20865127
J Virol. 2005 Apr;79(7):3987-97
pubmed: 15767401
J Virol. 1995 Jul;69(7):4037-44
pubmed: 7769661
Virus Genes. 2007 Jan;34(1):9-22
pubmed: 16927116
Rev Sci Tech. 2007 Aug;26(2):327-38
pubmed: 17892155
mSphere. 2019 Jan 16;4(1):
pubmed: 30651403
Avian Dis. 2016 Mar;60(1):22-32
pubmed: 26953940
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7279-84
pubmed: 26039998
PLoS Biol. 2015 Jul 27;13(7):e1002198
pubmed: 26214839
Cancers (Basel). 2020 Mar 10;12(3):
pubmed: 32164311
mSphere. 2019 Oct 9;4(5):
pubmed: 31597721
Epidemics. 2018 Jun;23:85-95
pubmed: 29366873
Annu Rev Virol. 2014 Nov;1(1):215-35
pubmed: 26958721
Avian Dis. 1997 Jan-Mar;41(1):149-63
pubmed: 9087332
Biochim Biophys Acta. 2016 Apr;1865(2):220-7
pubmed: 26951863
J Vet Diagn Invest. 2001 Mar;13(2):162-4
pubmed: 11289214
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11815-20
pubmed: 15289599
J Virol. 2012 Aug;86(16):8536-45
pubmed: 22647701
Avian Dis. 2016 Dec;60(4):715-724
pubmed: 27902902
Vaccine. 2008 Jul 18;26 Suppl 3:C31-41
pubmed: 18773529
J Virol Methods. 2006 Mar;132(1-2):127-34
pubmed: 16290211