Effect of Difference in Consensus Sequence between HIV-1 Subtype A/E and Subtype B Viruses on Elicitation of Gag-Specific CD8
Asian People
CD8-Positive T-Lymphocytes
/ immunology
Consensus Sequence
Epitopes, T-Lymphocyte
/ genetics
Genes, gag
/ genetics
HIV Infections
/ immunology
HIV-1
/ genetics
HLA-B Antigens
/ genetics
HLA-C Antigens
/ genetics
Humans
Immune Evasion
/ genetics
Mutation
T-Lymphocytes, Cytotoxic
/ immunology
Virus Replication
CTL
HIV-1
escape mutation
subtype A/E
subtype B
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
24 02 2021
24 02 2021
Historique:
received:
20
10
2020
accepted:
09
12
2020
pubmed:
29
12
2020
medline:
6
5
2021
entrez:
28
12
2020
Statut:
epublish
Résumé
The Gag280 mutation is associated with HLA-C*01:02 but not with HLA-B*52:01 in subtype A/E-infected individuals, whereas this mutation is associated with HLA-B*52:01 but not with HLA-C*01:02 in subtype B infections. Although it is known that the Gag280 mutant is selected by HLA-B*52:01-restricted GagRI8 (Gag275-282)-specific T cells in subtype B infections, it remains unknown why this Gag280 mutation is associated with HLA-C*01:02 rather than HLA-B*52:01 in subtype A/E infections. The subtype B and A/E viruses have different consensus sequence, with Thr and Val at Gag280, respectively. To clarify the effect of this difference in Gag280 consensus sequence, we investigated the role of HLA-C*01:02-restricted GagYI9 (Gag277-285)-specific T cells in selection of Gag280 mutations in subtype A/E-infected Vietnamese and subtype B-infected Japanese individuals. GagYI9-4V-specific T cells, which were frequently elicited in Vietnamese individuals infected with the consensus-type A/E virus, failed to recognize GagV280T mutant A/E virus-infected cells. GagYI9-4T mutant epitope-specific T cells, which were weakly elicited in individuals infected with the mutant A/E virus, had weak or no ability to recognize the mutant virus. These results account for the mechanism for selection and accumulation of GagV280T mutants in the case of subtype A/E infections. In contrast, HLA-C*01:02-restricted GagYI9-4T-specific T cells were weakly elicited in Japanese individuals infected with the subtype B virus, explaining why HLA-C*01:02-restricted Gag280 mutations are not accumulated in the case of a subtype B infection. The present study demonstrated that a difference in the Gag280 consensus sequence influenced the elicitation of the GagYI9-specific T cells involved in the accumulation of HLA-C*01:02-associated Gag280 mutations.
Identifiants
pubmed: 33361435
pii: JVI.02061-20
doi: 10.1128/JVI.02061-20
pmc: PMC8094948
pii:
doi:
Substances chimiques
Epitopes, T-Lymphocyte
0
HLA-B Antigens
0
HLA-C Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 Zhang et al.
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