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HLA class I-mediated HIV-1 control in Vietnamese infected with HIV-1 subtype A/E.

HLA class I-mediated HIV-1 control in Vietnamese infected with HIV-1 subtype A/E.
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Chikata T, Van Tran G, Murakoshi H, Akahoshi T, Qi Y, Naranbhai V, Kuse N, Tamura Y, Koyanagi M, Sakai S, Nguyen DH, Nguyen DT, Nguyen HT, Nguyen TV, Oka S, Martin MP, Carrington M, Sakai K, Van Nguyen K, Takiguchi M,


Chikata T, Van Tran G, Murakoshi H, Akahoshi T, Qi Y, Naranbhai V, Kuse N, Tamura Y, Koyanagi M, Sakai S, Nguyen DH, Nguyen DT, Nguyen HT, Nguyen TV, Oka S, Martin MP, Carrington M, Sakai K, Van Nguyen K, Takiguchi M, (click to view)

Chikata T, Van Tran G, Murakoshi H, Akahoshi T, Qi Y, Naranbhai V, Kuse N, Tamura Y, Koyanagi M, Sakai S, Nguyen DH, Nguyen DT, Nguyen HT, Nguyen TV, Oka S, Martin MP, Carrington M, Sakai K, Van Nguyen K, Takiguchi M,

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Journal of virology 2017 12 13() pii 10.1128/JVI.01749-17

Abstract

HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcome in treatment-naïve Vietnamese infected with subtype A/E. We found that HLA-C*12:02 was significantly associated with lower pVL and higher CD4 count and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 count as compared to individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, where a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL in individuals with these HLA alleles were observed. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affect HIV control.ImportanceMost previous studies on HLA association with disease progression after HIV-1 infection have been performed in cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have reported in cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes in 536 HIV-1 subtype A/E infected Vietnamese individuals. We found that HLA-C*12:02 is protective while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral load and lower CD4 counts than those without the mutations, suggesting viral adaptation and escape from HLA-mediated immune control. The present study identified a protective allele and a deleterious haplotype in the subtype A/E infection, which are different from those identified in cohorts infected with HIV-1 subtypes B and C.

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