Potent Enhancement of HIV-1 Replication by Nef in the Absence of SERINC3 and SERINC5.
CD4 Antigens
/ genetics
Cell Line
Endocytosis
Glycosylation
HIV-1
/ genetics
Host-Pathogen Interactions
Humans
Jurkat Cells
Membrane Glycoproteins
/ antagonists & inhibitors
Membrane Proteins
/ antagonists & inhibitors
Virus Replication
/ genetics
gag Gene Products, Human Immunodeficiency Virus
/ metabolism
nef Gene Products, Human Immunodeficiency Virus
/ genetics
Nef
SERINC5
human immunodeficiency virus
infectivity
virus replication
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
11 06 2019
11 06 2019
Historique:
entrez:
13
6
2019
pubmed:
13
6
2019
medline:
25
1
2020
Statut:
epublish
Résumé
It has recently emerged that HIV-1 Nef counteracts the antiviral host proteins SERINC3 and SERINC5. In particular, SERINC5 inhibits the infectivity of progeny virions when incorporated. SERINC3 and SERINC5 are also counteracted by the unrelated murine leukemia virus glycosylated Gag (glycoGag) protein, which possesses a potent Nef-like activity on HIV-1 infectivity. We now report that a minimal glycoGag termed glycoMA can fully substitute for Nef in promoting HIV-1 replication in Jurkat T lymphoid cells, indicating that Nef enhances replication in these cells mainly by counteracting SERINCs. In contrast, the SERINC antagonist glycoMA was unable to substitute for Nef in MOLT-3 T lymphoid cells, in which HIV-1 replication was highly dependent on Nef, and remained so even in the absence of SERINC3 and SERINC5. As in MOLT-3 cells, glycoMA was unable to substitute for Nef in stimulating HIV-1 replication in primary human cells. Although the ability of Nef mutants to promote HIV-1 replication in MOLT-3 cells correlated with the ability to engage endocytic machinery and to downregulate CD4, Nef nevertheless rescued virus replication under conditions where CD4 downregulation did not occur. Taken together, our observations raise the possibility that Nef triggers the endocytosis of a novel antiviral factor that is active against both laboratory-adapted and primary HIV-1 strains.
Identifiants
pubmed: 31186327
pii: mBio.01071-19
doi: 10.1128/mBio.01071-19
pmc: PMC6561029
pii:
doi:
Substances chimiques
CD4 Antigens
0
Membrane Glycoproteins
0
Membrane Proteins
0
SERINC3 protein, human
0
SERINC5 protein, human
0
gag Gene Products, Human Immunodeficiency Virus
0
nef Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI127263
Pays : United States
Informations de copyright
Copyright © 2019 Wu et al.
Références
J Exp Med. 1994 Jan 1;179(1):115-23
pubmed: 7903679
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11229-34
pubmed: 9736718
J Virol. 2014 Mar;88(6):3443-54
pubmed: 24403584
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7290-5
pubmed: 10852971
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9544-8
pubmed: 2687883
Cell Rep. 2013 Nov 14;5(3):802-12
pubmed: 24209751
J Immunol. 2005 Nov 1;175(9):6050-7
pubmed: 16237100
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6812-7
pubmed: 17412836
J Virol. 1995 Jul;69(7):4413-22
pubmed: 7769703
Nature. 1991 Apr 11;350(6318):508-11
pubmed: 2014052
J Biol Chem. 1999 Oct 1;274(40):28745-50
pubmed: 10497246
J Virol. 2006 Feb;80(4):1837-49
pubmed: 16439540
PLoS Pathog. 2018 Aug 20;14(8):e1007269
pubmed: 30125328
Nat Med. 1996 Mar;2(3):338-42
pubmed: 8612235
J Virol. 1994 May;68(5):2906-14
pubmed: 8151761
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7093-7098
pubmed: 29891700
Nature. 2015 Oct 8;526(7572):212-7
pubmed: 26416734
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):394-9
pubmed: 10618429
Curr Biol. 1999 Jun 17;9(12):613-21
pubmed: 10375525
Cell Rep. 2018 Jan 23;22(4):869-875
pubmed: 29386131
J Virol. 2010 Jul;84(13):6425-37
pubmed: 20410271
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13197-13202
pubmed: 27803322
Science. 1995 Nov 10;270(5238):988-91
pubmed: 7481804
J Virol. 2017 Jan 31;91(4):
pubmed: 27928004
J Virol. 1995 Jan;69(1):579-84
pubmed: 7983759
J Biol Chem. 2017 Apr 7;292(14):6014-6026
pubmed: 28179429
Nature. 2015 Oct 8;526(7572):218-23
pubmed: 26416733
Cell Host Microbe. 2016 Sep 14;20(3):381-391
pubmed: 27631701
Cell Host Microbe. 2015 Oct 14;18(4):409-23
pubmed: 26439863
EMBO J. 1997 Feb 17;16(4):673-84
pubmed: 9049297
J Virol. 1995 Aug;69(8):5048-56
pubmed: 7541845
J Virol. 1993 Mar;67(3):1511-6
pubmed: 8437228
J Virol. 2004 Jul;78(13):6915-26
pubmed: 15194768
Virology. 1990 Jun;176(2):413-25
pubmed: 2111956
J Virol. 2008 Feb;82(3):1166-74
pubmed: 18032517
Cell. 1994 Mar 11;76(5):853-64
pubmed: 8124721
mBio. 2016 Nov 22;7(6):
pubmed: 27879338
Curr Biol. 1998 Nov 5;8(22):1235-8
pubmed: 9811606
J Exp Med. 1994 Jan 1;179(1):101-13
pubmed: 8270859
J Biol Chem. 2000 Jul 28;275(30):23097-105
pubmed: 10807905
J Virol. 2008 Nov;82(21):10811-9
pubmed: 18715908
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13567-72
pubmed: 14597713
Cell. 1991 May 17;65(4):651-62
pubmed: 2032289
J Virol. 1996 Nov;70(11):7752-64
pubmed: 8892896
J Virol. 2002 May;76(9):4625-33
pubmed: 11932428
Curr Biol. 1999 Jun 17;9(12):622-31
pubmed: 10375528
Future Virol. 2013 Apr 1;8(4):
pubmed: 24187576
J Virol. 2001 Feb;75(4):1672-80
pubmed: 11160665
EMBO J. 1995 Feb 1;14(3):484-91
pubmed: 7859737
J Virol. 1995 Jul;69(7):4053-9
pubmed: 7539505
J Mol Biol. 2009 Nov 27;394(2):329-42
pubmed: 19781555
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9364-9
pubmed: 20439730
J Virol. 2007 Dec;81(24):13852-64
pubmed: 17928336
Virology. 1996 Mar 1;217(1):293-300
pubmed: 8599214