A Conserved Acidic-Cluster Motif in SERINC5 Confers Partial Resistance to Antagonism by HIV-1 Nef.
Alleles
Amino Acid Motifs
Cytoplasm
/ metabolism
Gene Deletion
Glycosylation
HEK293 Cells
HIV-1
HeLa Cells
Humans
Infectious Anemia Virus, Equine
/ metabolism
Jurkat Cells
Membrane Proteins
/ chemistry
Moloney murine leukemia virus
/ metabolism
Mutation
Protein Domains
nef Gene Products, Human Immunodeficiency Virus
/ genetics
HIV-1
Nef
SERINC
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
17 03 2020
17 03 2020
Historique:
received:
11
09
2019
accepted:
12
01
2020
pubmed:
17
1
2020
medline:
15
9
2020
entrez:
17
1
2020
Statut:
epublish
Résumé
The cellular protein SERINC5 inhibits the infectivity of diverse retroviruses, and its activity is counteracted by the glycosylated Gag (glycoGag) protein of murine leukemia virus (MLV), the S2 protein of equine infectious anemia virus (EIAV), and the Nef protein of human immunodeficiency virus type 1 (HIV-1). Determining the regions within SERINC5 that provide restrictive activity or Nef sensitivity should inform mechanistic models of the SERINC5/HIV-1 relationship. Here, we report that deletion of the conserved sequence EDTEE, which is located within a cytoplasmic loop of SERINC5 and which is reminiscent of an acidic-cluster membrane trafficking signal, increases the sensitivity of SERINC5 to antagonism by Nef, while it has no effect on the intrinsic activity of the protein as an inhibitor of infectivity. These effects correlated with enhanced removal of the ΔEDTEE mutant relative to that of wild-type SERINC5 from the cell surface and with enhanced exclusion of the mutant protein from virions by Nef. Mutational analysis indicated that the acidic residues, but not the threonine, within the EDTEE motif are important for the relative resistance to Nef. Deletion of the EDTEE sequence did not increase the sensitivity of SERINC5 to antagonism by the glycoGag protein of MLV, suggesting that its virologic role is Nef specific. These results are consistent with the reported mapping of the cytoplasmic loop that contains the EDTEE sequence as a general determinant of Nef responsiveness, but they further indicate that sequences inhibitory to as well as supportive of Nef activity reside in this region. We speculate that the EDTEE motif might have evolved to mediate resistance against retroviruses that use Nef-like proteins to antagonize SERINC5.
Identifiants
pubmed: 31941773
pii: JVI.01554-19
doi: 10.1128/JVI.01554-19
pmc: PMC7081897
pii:
doi:
Substances chimiques
Membrane Proteins
0
SERINC5 protein, human
0
nef Gene Products, Human Immunodeficiency Virus
0
nef protein, Human immunodeficiency virus 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : K12 GM068524
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI036214
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129706
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
Références
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9544-8
pubmed: 2687883
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13197-13202
pubmed: 27803322
Cell Rep. 2013 Nov 14;5(3):802-12
pubmed: 24209751
J Virol. 2008 Apr;82(8):3952-70
pubmed: 18256145
J Virol. 2018 May 14;92(11):
pubmed: 29514909
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6812-7
pubmed: 17412836
J Virol. 1995 Aug;69(8):5048-56
pubmed: 7541845
J Virol. 2019 Nov 26;93(24):
pubmed: 31597782
J Virol. 2005 Oct;79(20):12732-41
pubmed: 16188976
Immunity. 1998 Apr;8(4):483-95
pubmed: 9586638
J Virol. 2001 Apr;75(8):3657-65
pubmed: 11264355
J Virol. 2007 Dec;81(24):13852-64
pubmed: 17928336
J Theor Biol. 2009 Nov 21;261(2):341-60
pubmed: 19660475
J Virol. 1994 May;68(5):2906-14
pubmed: 8151761
J Virol. 2016 Aug 26;90(18):8085-9
pubmed: 27356902
J Virol. 2007 Apr;81(8):3877-90
pubmed: 17267500
Nat Med. 1996 Mar;2(3):338-42
pubmed: 8612235
J Biol Chem. 2017 Feb 17;292(7):2670-2678
pubmed: 28031466
Retrovirology. 2014 Feb 06;11:15
pubmed: 24498878
J Virol. 2018 Oct 29;92(22):
pubmed: 30158294
J Exp Med. 1994 Jan 1;179(1):115-23
pubmed: 7903679
J Virol Methods. 2006 Oct;137(1):125-33
pubmed: 16876264
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11229-34
pubmed: 9736718
J Virol. 1996 Jul;70(7):4283-90
pubmed: 8676450
Nature. 2015 Oct 8;526(7572):212-7
pubmed: 26416734
Cell Host Microbe. 2010 Jul 22;8(1):55-67
pubmed: 20638642
Retrovirology. 2015 Jul 28;12:65
pubmed: 26215564
J Virol. 1992 Dec;66(12):7193-200
pubmed: 1433512
J Virol. 2014 Mar;88(6):3443-54
pubmed: 24403584
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5011-5
pubmed: 1711215
Cell Rep. 2018 Jan 23;22(4):869-875
pubmed: 29386131
J Virol. 1992 Jan;66(1):226-34
pubmed: 1727486
Curr Biol. 1999 Jun 17;9(12):613-21
pubmed: 10375525
N Engl J Med. 1995 Jan 26;332(4):228-32
pubmed: 7808489
Nature. 1987 Nov 19-25;330(6145):266-9
pubmed: 3118220
Nature. 1998 Jan 22;391(6665):397-401
pubmed: 9450757
J Virol. 2006 Aug;80(16):8047-59
pubmed: 16873261
Cell. 2002 Dec 13;111(6):853-66
pubmed: 12526811
J Virol. 1986 Aug;59(2):284-91
pubmed: 3016298
J Virol. 2017 Jan 31;91(4):
pubmed: 27928004
J Biol Chem. 2005 Oct 21;280(42):35776-83
pubmed: 16120614
J Virol. 1995 Jan;69(1):579-84
pubmed: 7983759
J Biol Chem. 2017 Apr 7;292(14):6014-6026
pubmed: 28179429
J Virol. 2006 Feb;80(3):1311-20
pubmed: 16415008
Nature. 2015 Oct 8;526(7572):218-23
pubmed: 26416733
Cell. 1994 Mar 11;76(5):853-64
pubmed: 8124721
Science. 1992 Nov 27;258(5087):1485-8
pubmed: 1359646
J Virol. 2019 Jan 4;93(2):
pubmed: 30355687
J Biol Chem. 2018 Oct 5;293(40):15678-15690
pubmed: 30135209
J Virol. 2009 Jul;83(13):6578-90
pubmed: 19403684
J Biol Chem. 2017 Aug 18;292(33):13702-13713
pubmed: 28659343
Cell. 1999 Apr 2;97(1):63-73
pubmed: 10199403
Cell. 1991 May 17;65(4):651-62
pubmed: 2032289
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
pubmed: 18490657
J Virol. 2014 Mar;88(5):2633-44
pubmed: 24352444
J Cell Biol. 2004 Dec 6;167(5):903-13
pubmed: 15569716
Cell. 2010 Jun 25;141(7):1220-9
pubmed: 20603002
Nat Struct Mol Biol. 2012 Jun 17;19(7):701-6
pubmed: 22705789
J Exp Med. 2009 Jun 8;206(6):1273-89
pubmed: 19487424
J Virol. 2012 Mar;86(5):2715-28
pubmed: 22190722
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9364-9
pubmed: 20439730