Characterization of a multipurpose NS3 surface patch coordinating HCV replicase assembly and virion morphogenesis.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
09
06
2022
accepted:
25
09
2022
revised:
28
10
2022
pubmed:
11
10
2022
medline:
2
11
2022
entrez:
10
10
2022
Statut:
epublish
Résumé
The hepatitis C virus (HCV) life cycle is highly regulated and characterized by a step-wise succession of interactions between viral and host cell proteins resulting in the assembly of macromolecular complexes, which catalyse genome replication and/or virus production. Non-structural (NS) protein 3, comprising a protease and a helicase domain, is involved in orchestrating these processes by undergoing protein interactions in a temporal fashion. Recently, we identified a multifunctional NS3 protease surface patch promoting pivotal protein-protein interactions required for early steps of the HCV life cycle, including NS3-mediated NS2 protease activation and interactions required for replicase assembly. In this work, we extend this knowledge by identifying further NS3 surface determinants important for NS5A hyperphosphorylation, replicase assembly or virion morphogenesis, which map to protease and helicase domain and form a contiguous NS3 surface area. Functional interrogation led to the identification of phylogenetically conserved amino acid positions exerting a critical function in virion production without affecting RNA replication. These findings illustrate that NS3 uses a multipurpose protein surface to orchestrate the step-wise assembly of functionally distinct multiprotein complexes. Taken together, our data provide a basis to dissect the temporal formation of viral multiprotein complexes required for the individual steps of the HCV life cycle.
Identifiants
pubmed: 36215335
doi: 10.1371/journal.ppat.1010895
pii: PPATHOGENS-D-22-01017
pmc: PMC9616216
doi:
Substances chimiques
Viral Nonstructural Proteins
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010895Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Virol. 2014 Sep;88(18):10970-4
pubmed: 24965468
J Viral Hepat. 2011 May;18(5):305-15
pubmed: 21470343
J Virol. 2010 Sep;84(18):9267-77
pubmed: 20592076
Nucleic Acids Res. 2004 Oct 12;32(18):5519-28
pubmed: 15479787
J Virol. 2017 Feb 28;91(6):
pubmed: 28053108
J Virol. 2011 Nov;85(21):11022-37
pubmed: 21849455
PLoS Pathog. 2016 Jan 04;12(1):e1005376
pubmed: 26727512
J Virol. 2007 May;81(9):4591-603
pubmed: 17301154
J Virol. 2009 Apr;83(7):3268-75
pubmed: 19153239
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5342-7
pubmed: 19282477
J Virol. 2019 Dec 12;94(1):
pubmed: 31597774
PLoS Pathog. 2015 Apr 13;11(4):e1004817
pubmed: 25875808
Cell Rep. 2019 Jun 18;27(12):3602-3617.e5
pubmed: 31216478
Cells. 2019 May 22;8(5):
pubmed: 31121874
J Gen Virol. 2009 Jun;90(Pt 6):1329-1334
pubmed: 19264615
mBio. 2018 Mar 13;9(2):
pubmed: 29535204
J Gen Virol. 2017 Aug;98(8):2106-2112
pubmed: 28786787
PLoS Pathog. 2015 Jan 08;11(1):e1004573
pubmed: 25569684
Nat Chem Biol. 2012 Nov;8(11):920-5
pubmed: 23023261
J Virol. 2003 Mar;77(5):3181-90
pubmed: 12584342
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13038-43
pubmed: 15326295
J Virol. 2007 Jan;81(2):629-38
pubmed: 17079282
J Virol. 2004 Dec;78(23):13278-84
pubmed: 15542678
J Virol. 2003 Mar;77(5):3007-19
pubmed: 12584326
J Virol. 2009 Oct;83(20):10788-96
pubmed: 19656877
PLoS Pathog. 2009 May;5(5):e1000403
pubmed: 19412343
Curr Issues Mol Biol. 2007 Jan;9(1):63-9
pubmed: 17263146
J Virol. 1994 Aug;68(8):5045-55
pubmed: 8035505
PLoS Pathog. 2007 Jul;3(7):e103
pubmed: 17658949
J Virol. 2013 Oct;87(19):10612-27
pubmed: 23885072
Science. 1999 Jul 2;285(5424):110-3
pubmed: 10390360
J Virol. 2015 Dec 30;90(6):2868-83
pubmed: 26719260
J Virol. 2015 Apr;89(8):4562-74
pubmed: 25673706
J Virol. 2009 Dec;83(24):12702-13
pubmed: 19812162
Structure. 1999 Nov 15;7(11):1353-63
pubmed: 10574797
J Virol. 2008 Feb;82(3):1073-83
pubmed: 18032500
J Virol. 2011 Jul;85(14):6963-76
pubmed: 21543474
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5547-51
pubmed: 1648221
J Virol. 1993 Mar;67(3):1385-95
pubmed: 7679746
J Virol. 2008 Jan;82(1):173-83
pubmed: 17942558
J Virol. 2009 Sep;83(17):8379-95
pubmed: 19515772
Nat Rev Microbiol. 2013 Oct;11(10):688-700
pubmed: 24018384
Cell Host Microbe. 2011 Jan 20;9(1):32-45
pubmed: 21238945
J Virol. 1999 Sep;73(9):7138-46
pubmed: 10438800
J Biol Chem. 2008 Oct 31;283(44):29929-37
pubmed: 18723512
PLoS Pathog. 2018 Feb 7;14(2):e1006863
pubmed: 29415072
PLoS Pathog. 2010 Dec 16;6(12):e1001233
pubmed: 21187906
J Gen Virol. 2004 Jun;85(Pt 6):1497-1507
pubmed: 15166434
J Virol. 1994 Aug;68(8):5063-73
pubmed: 7518529
J Virol. 1996 Feb;70(2):1041-9
pubmed: 8551562
J Virol. 2014 Jan;88(1):628-42
pubmed: 24173222
J Virol. 2015 May;89(10):5462-77
pubmed: 25740981
J Biol Chem. 2004 Nov 19;279(47):48576-87
pubmed: 15339921
Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21052-6
pubmed: 22160684
PLoS Pathog. 2012;8(3):e1002598
pubmed: 22457622
J Virol. 2008 Jun;82(12):5715-24
pubmed: 18367533
J Virol. 1994 Nov;68(11):7525-33
pubmed: 7933136
J Biol Chem. 2005 Aug 19;280(33):29604-11
pubmed: 15980068
J Virol. 2011 Feb;85(3):1193-204
pubmed: 21047963
Annu Rev Virol. 2015 Nov;2(1):289-310
pubmed: 26958917
J Virol. 2008 Apr;82(7):3342-52
pubmed: 18199634
Curr Top Microbiol Immunol. 2013;369:113-42
pubmed: 23463199
J Mol Biol. 2010 Jul 16;400(3):354-78
pubmed: 20451531
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10773-7
pubmed: 7504283
J Biol Chem. 2007 Nov 30;282(48):34913-20
pubmed: 17921146
Virology. 2002 Jan 20;292(2):198-210
pubmed: 11878923
Science. 2005 Jul 22;309(5734):623-6
pubmed: 15947137
EMBO J. 2002 Aug 1;21(15):3980-8
pubmed: 12145199
Trends Microbiol. 2011 Feb;19(2):95-103
pubmed: 21146993
J Biol Chem. 2004 Jan 9;279(2):1269-80
pubmed: 14585830
Hepatology. 1999 Apr;29(4):1227-35
pubmed: 10094969
J Virol. 2022 Apr 13;96(7):e0010722
pubmed: 35293767
Virology. 2004 Jul 1;324(2):450-61
pubmed: 15207630
J Virol. 2011 Aug;85(16):8158-71
pubmed: 21680530
J Virol. 1999 Dec;73(12):9984-91
pubmed: 10559312
J Virol. 2008 Aug;82(16):7964-76
pubmed: 18524832
FEBS Lett. 1995 Aug 28;371(1):9-12
pubmed: 7664891
Virology. 2015 Jan 15;475:139-49
pubmed: 25462354
PLoS Pathog. 2015 Mar 16;11(3):e1004736
pubmed: 25774920
J Virol. 2007 May;81(10):5270-83
pubmed: 17344294
J Virol. 2008 Nov;82(21):10671-83
pubmed: 18715921
Virology. 1999 Sep 15;262(1):250-63
pubmed: 10489358
Nucleic Acids Res. 1990 Nov 11;18(21):6464
pubmed: 2173834
J Virol. 2007 Sep;81(17):8905-18
pubmed: 17581983
J Virol. 2007 Jun;81(11):5724-36
pubmed: 17360748
J Virol. 2005 Jul;79(14):8687-97
pubmed: 15994762
Nat Med. 2005 Jul;11(7):791-6
pubmed: 15951748
J Gen Virol. 2009 May;90(Pt 5):1071-1080
pubmed: 19264595
J Exp Med. 2003 Mar 3;197(5):633-42
pubmed: 12615904
Adv Virus Res. 2015;93:47-160
pubmed: 26111586
J Virol. 2015 Apr;89(8):4356-71
pubmed: 25653438
J Virol. 2002 Nov;76(21):10766-75
pubmed: 12368319
J Mol Biol. 2011 Feb 4;405(5):1139-53
pubmed: 21145896
J Virol. 2005 Nov;79(21):13778-93
pubmed: 16227297
J Biol Chem. 2008 Oct 17;283(42):28546-62
pubmed: 18644781
J Virol. 2011 Feb;85(4):1706-17
pubmed: 21147927
J Virol. 2011 Jan;85(1):86-97
pubmed: 20962101
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14545-50
pubmed: 18799730
Anal Biochem. 1987 Nov 1;166(2):368-79
pubmed: 2449095
PLoS Pathog. 2013;9(5):e1003355
pubmed: 23658526
J Virol. 1994 Jun;68(6):3753-60
pubmed: 8189513
J Gen Virol. 2013 May;94(Pt 5):1009-1018
pubmed: 23324467
Protein Sci. 2013 Dec;22(12):1786-98
pubmed: 24123290
J Virol. 2008 Aug;82(15):7624-39
pubmed: 18508894
J Virol. 2011 May;85(9):4343-53
pubmed: 21325413
J Virol. 2014 Nov;88(21):12422-37
pubmed: 25122793
PLoS Pathog. 2011 Feb 10;7(2):e1001278
pubmed: 21347350
Nat Med. 2013 Jun;19(6):722-9
pubmed: 23708292
J Virol. 2011 Dec;85(23):12351-61
pubmed: 21957313
Biochemistry. 2010 Mar 16;49(10):2097-109
pubmed: 20108974
EMBO J. 1996 Jan 2;15(1):12-22
pubmed: 8598194