Valosin-containing protein/p97 plays critical roles in the Japanese encephalitis virus life cycle.
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
10 05 2021
10 05 2021
Historique:
entrez:
18
3
2021
pubmed:
19
3
2021
medline:
19
3
2021
Statut:
ppublish
Résumé
Host factors provide critical support for every aspect of the virus life cycle. We recently identified the valosin-containing protein (VCP)/p97, an abundant cellular ATPase with diverse cellular functions, as a host factor important for Japanese encephalitis virus (JEV) replication. In cultured cells, using siRNA-mediated protein depletion and pharmacological inhibitors, we show that VCP is crucial for replication of three flaviviruses: JEV, Dengue, and West Nile viruses. An FDA-approved VCP inhibitor, CB-5083, extended survival of mice in the animal model of JEV infection. While VCP depletion did not inhibit JEV attachment on cells, it delayed capsid degradation, potentially through the entrapment of the endocytosed virus in clathrin-coated vesicles (CCVs). Early during infection, VCP-depleted cells showed an increased colocalization of JEV capsid with clathrin, and also higher viral RNA levels in purified CCVs. We show that VCP interacts with the JEV nonstructural protein NS5 and is an essential component of the virus replication complex. The depletion of the major VCP cofactor UFD-1 also significantly inhibited JEV replication. Mechanistically, thus, VCP affected two crucial steps of the JEV life cycle - nucleocapsid release and RNA replication. Our study establishes VCP as a common host factor with a broad antiviral potential against flaviviruses.
Identifiants
pubmed: 33731458
pii: JVI.02336-20
doi: 10.1128/JVI.02336-20
pmc: PMC8139707
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 American Society for Microbiology.
Références
Nature. 1993 Sep 30;365(6445):459-62
pubmed: 8413590
Viruses. 2011 Feb;3(2):160-71
pubmed: 22049308
EMBO J. 2000 May 15;19(10):2181-92
pubmed: 10811609
J Virol. 2017 Oct 13;91(21):
pubmed: 28794043
J Cell Sci. 2014 Sep 15;127(Pt 18):3877-83
pubmed: 25146396
Cold Spring Harb Protoc. 2015 Nov 02;2015(11):1013-6
pubmed: 26527762
Mol Cell. 2014 Mar 20;53(6):893-903
pubmed: 24613342
Cell Host Microbe. 2009 Apr 23;5(4):318-28
pubmed: 19380111
Cold Spring Harb Protoc. 2015 Dec 02;2015(12):pdb.top074443
pubmed: 26631131
Biochem J. 2017 Aug 17;474(17):2953-2976
pubmed: 28819009
Nat Cell Biol. 2011 Aug 07;13(9):1116-23
pubmed: 21822278
PLoS One. 2014 Dec 29;9(12):e114931
pubmed: 25545659
Science. 2014 Oct 24;346(6208):473-7
pubmed: 25342804
Viruses. 2019 Jan 15;11(1):
pubmed: 30650657
J Virol. 2016 Oct 14;90(21):9953-9966
pubmed: 27558430
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17516-21
pubmed: 24101521
Trends Biochem Sci. 2011 Oct;36(10):515-23
pubmed: 21741246
EMBO J. 2015 Dec 2;34(23):2903-20
pubmed: 26471729
Cell Biosci. 2013 May 23;3(1):24
pubmed: 23701900
J Virol. 2017 Feb 28;91(6):
pubmed: 28053106
Mol Cancer Ther. 2017 Nov;16(11):2375-2386
pubmed: 28878026
Nat Genet. 2004 Apr;36(4):377-81
pubmed: 15034582
Microbiol Immunol. 1993;37(3):239-43
pubmed: 8321152
Nat Rev Microbiol. 2018 Feb 12;16(3):125-142
pubmed: 29430005
Virus Res. 2017 Jan 15;228:114-123
pubmed: 27914931
Nat Rev Microbiol. 2008 May;6(5):363-74
pubmed: 18414501
Front Mol Biosci. 2017 Jun 13;4:39
pubmed: 28660197
Rev Med Virol. 2016 May;26(3):146-60
pubmed: 26817660
Cold Spring Harb Protoc. 2014 Nov 03;2014(11):1184-7
pubmed: 25368312
Autophagy. 2014 Sep;10(9):1637-51
pubmed: 25046112
J Gen Virol. 2021 Jan;102(1):
pubmed: 33095129
Nat Rev Microbiol. 2005 Jan;3(1):13-22
pubmed: 15608696
Biochem Biophys Res Commun. 2007 Mar 9;354(2):459-65
pubmed: 17239345
Virus Res. 2015 May 4;203:84-91
pubmed: 25865411
Nat Commun. 2016 Oct 17;7:13150
pubmed: 27748395
Molecules. 2015 Feb 12;20(2):3027-49
pubmed: 25685910
J Med Chem. 2015 Dec 24;58(24):9480-97
pubmed: 26565666
Virus Res. 2020 Jul 2;283:197974
pubmed: 32289342
Cell Rep. 2012 Oct 25;2(4):1036-47
pubmed: 23084750
Lancet. 2008 Feb 9;371(9611):500-9
pubmed: 18262042
J Virol. 2012 May;86(10):5541-53
pubmed: 22379090
Curr Mol Med. 2017;17(9):608-618
pubmed: 29521227
Mol Cell. 2018 Jan 18;69(2):182-194
pubmed: 29153394
mBio. 2020 Apr 14;11(2):
pubmed: 32291299
J Mol Biol. 2018 Jun 22;430(13):1853-1862
pubmed: 29709571
Cell Rep. 2013 Dec 26;5(6):1737-48
pubmed: 24332855
Cancer Cell. 2017 Mar 13;31(3):311-325
pubmed: 28292435
Biochim Biophys Acta. 2012 Jan;1823(1):138-44
pubmed: 21807033
J Virol. 2015 Nov;89(21):11116-28
pubmed: 26311884
J Gen Virol. 2019 Feb;100(2):176-186
pubmed: 30489239
PLoS Pathog. 2017 May 11;13(5):e1006329
pubmed: 28494016
Cold Spring Harb Protoc. 2015 Nov 02;2015(11):1009-12
pubmed: 26527761
Virol J. 2016 Jul 29;13:131
pubmed: 27473856
Microb Pathog. 2020 Dec;149:104565
pubmed: 33059057
J Gen Virol. 2017 Jul;98(7):1667-1678
pubmed: 28691899
mBio. 2016 Jun 28;7(3):
pubmed: 27353759
Mol Oncol. 2016 Dec;10(10):1559-1574
pubmed: 27729194
Front Microbiol. 2019 Sep 24;10:2236
pubmed: 31636613
Cell Res. 2012 Feb;22(2):346-59
pubmed: 21556036
J Struct Biol. 2012 Aug;179(2):78-82
pubmed: 22450227