T-cell responses to sequentially emerging viral escape mutants shape long-term HIV-1 population dynamics.
Antigenic Variation
/ immunology
Cells, Cultured
Clonal Evolution
/ immunology
Epitopes, T-Lymphocyte
/ genetics
HIV Infections
/ immunology
HIV Seropositivity
HIV-1
/ classification
HeLa Cells
Host Adaptation
/ immunology
Host-Pathogen Interactions
/ genetics
Humans
Immune Evasion
/ genetics
Molecular Typing
Mutation
T-Lymphocytes, Cytotoxic
/ immunology
Viral Load
/ immunology
Virus Replication
/ genetics
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:
25
09
2020
accepted:
18
11
2020
revised:
25
01
2021
pubmed:
29
12
2020
medline:
26
3
2021
entrez:
28
12
2020
Statut:
epublish
Résumé
HIV-1 strains harboring immune escape mutations can persist in circulation, but the impact of selection by multiple HLA alleles on population HIV-1 dynamics remains unclear. In Japan, HIV-1 Reverse Transcriptase codon 135 (RT135) is under strong immune pressure by HLA-B*51:01-restricted and HLA-B*52:01-restricted T cells that target a key epitope in this region (TI8; spanning RT codons 128-135). Major population-level shifts have occurred at HIV-1 RT135 during the Japanese epidemic, which first affected hemophiliacs (via imported contaminated blood products) and subsequently non-hemophiliacs (via domestic transmission). Specifically, threonine accumulated at RT135 (RT135T) in hemophiliac and non-hemophiliac HLA-B*51:01+ individuals diagnosed before 1997, but since then RT135T has markedly declined while RT135L has increased among non-hemophiliac individuals. We demonstrated that RT135V selection by HLA-B*52:01-restricted TI8-specific T-cells led to the creation of a new HLA-C*12:02-restricted epitope TN9-8V. We further showed that TN9-8V-specific HLA-C*12:02-restricted T cells selected RT135L while TN9-8T-specific HLA-C*12:02-restricted T cells suppressed replication of the RT135T variant. Thus, population-level accumulation of the RT135L mutation over time in Japan can be explained by initial targeting of the TI8 epitope by HLA-B*52:01-restricted T-cells, followed by targeting of the resulting escape mutant by HLA-C*12:02-restricted T-cells. We further demonstrate that this phenomenon is particular to Japan, where the HLA-B*52:01-C*12:02 haplotype is common: RT135L did not accumulate over a 15-year longitudinal analysis of HIV sequences in British Columbia, Canada, where this haplotype is rare. Together, our observations reveal that T-cell responses to sequentially emerging viral escape mutants can shape long-term HIV-1 population dynamics in a host population-specific manner.
Identifiants
pubmed: 33370400
doi: 10.1371/journal.ppat.1009177
pii: PPATHOGENS-D-20-02119
pmc: PMC7833229
doi:
Substances chimiques
Epitopes, T-Lymphocyte
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009177Subventions
Organisme : CIHR
ID : PJT-148621
Pays : Canada
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
PLoS Pathog. 2019 Aug 9;15(8):e1007970
pubmed: 31398241
PLoS One. 2009 Aug 19;4(8):e6687
pubmed: 19690614
J Virol. 2012 Dec;86(24):13202-16
pubmed: 23055555
Trends Mol Med. 2001 Sep;7(9):379-81
pubmed: 11530315
Microbiol Immunol. 1988;32(8):851-5
pubmed: 3143898
Nat Med. 2016 Jun;22(6):606-13
pubmed: 27183217
Nature. 2009 Apr 2;458(7238):641-5
pubmed: 19242411
J Virol. 2017 Jan 31;91(4):
pubmed: 27903797
J Virol. 2005 Oct;79(20):12952-60
pubmed: 16188997
PLoS Genet. 2014 Apr 24;10(4):e1004295
pubmed: 24762668
J Immunol. 2005 Jun 15;174(12):7524-30
pubmed: 15944251
J Exp Med. 2006 May 15;203(5):1357-69
pubmed: 16682496
Science. 1996 Oct 4;274(5284):94-6
pubmed: 8810254
J Virol. 2019 Mar 21;93(7):
pubmed: 30674626
PLoS Pathog. 2007 Jul;3(7):e94
pubmed: 17616974
J Immunol. 2014 Jul 1;193(1):77-84
pubmed: 24899498
Cell Rep. 2016 Jun 7;15(10):2279-2291
pubmed: 27239036
J Virol. 2005 Nov;79(21):13239-49
pubmed: 16227247
J Immunol. 2011 Jul 15;187(2):684-91
pubmed: 21670313
J Infect Dis. 2017 Dec 12;216(11):1415-1424
pubmed: 28968792
J Virol. 2015 Jul;89(14):7363-72
pubmed: 25972553
J Exp Med. 2005 Mar 21;201(6):891-902
pubmed: 15781581
Tissue Antigens. 2000 Dec;56(6):522-9
pubmed: 11169242
Nat Med. 2004 Mar;10(3):229-30
pubmed: 14991039
Virology. 2006 Jan 20;344(2):354-62
pubmed: 16219331
Eur J Immunol. 2011 Jan;41(1):97-106
pubmed: 21182081
J Virol. 2006 Oct;80(19):9519-29
pubmed: 16973556
J Exp Med. 2009 Apr 13;206(4):909-21
pubmed: 19307327
Trends Microbiol. 2015 Apr;23(4):212-24
pubmed: 25613992
J Immunol. 1982 Jun;128(6):2804-6
pubmed: 6176653
J Virol. 2013 Feb;87(4):2253-63
pubmed: 23236061
Nat Med. 2004 Mar;10(3):282-9
pubmed: 14770175
Curr Opin Immunol. 2004 Aug;16(4):470-6
pubmed: 15245741
Science. 2010 Dec 10;330(6010):1551-7
pubmed: 21051598
J Virol. 2002 Aug;76(15):7535-43
pubmed: 12097566
J Virol. 2015 May;89(10):5330-9
pubmed: 25741000
Retrovirology. 2014 Aug 29;11:64
pubmed: 25212686
J Virol. 2008 Jul;82(13):6434-46
pubmed: 18434400
J Virol. 2012 Oct;86(19):10870-2
pubmed: 22811530
Virology. 2014 Feb;450-451:34-48
pubmed: 24503065
J Virol. 2007 Jan;81(1):193-201
pubmed: 17065207
Br J Haematol. 1987 Feb;65(2):249-50
pubmed: 3644665
EBioMedicine. 2018 Oct;36:103-112
pubmed: 30249546
Cell Rep. 2016 Nov 22;17(9):2210-2220
pubmed: 27880898
J Virol. 2010 Jul;84(14):7151-60
pubmed: 20410273
Microbiol Immunol. 2010 Apr;54(4):196-205
pubmed: 20377748
Tissue Antigens. 2015 Apr;85(4):252-9
pubmed: 25789826
Nat Med. 2004 Mar;10(3):275-81
pubmed: 14966520
J Virol. 2015 Nov 11;90(3):1244-58
pubmed: 26559841
Nat Med. 1997 Feb;3(2):212-7
pubmed: 9018241
PLoS One. 2008 Jun 18;3(6):e2422
pubmed: 18560583
PLoS One. 2013 Dec 03;8(12):e80045
pubmed: 24312453
Nature. 2001 Jul 19;412(6844):334-8
pubmed: 11460164
J Exp Med. 2001 Feb 5;193(3):375-86
pubmed: 11157057
AIDS. 2018 Sep 10;32(14):1927-1938
pubmed: 30048246
J Immunol. 2014 Nov 15;193(10):4814-22
pubmed: 25305317
J Exp Med. 2016 Sep 19;213(10):2049-63
pubmed: 27551154
Retrovirology. 2009 Aug 10;6:72
pubmed: 19664284
PLoS Pathog. 2010 Nov 18;6(11):e1001196
pubmed: 21124991
Science. 2002 May 24;296(5572):1439-43
pubmed: 12029127