Impaired protective role of HLA-B57:01/58:01 in HIV-1 CRF01_AE infection: a cohort study in Vietnam

• Published in: International journal of infectious diseases 2023-03, Vol.128, p.20-31
• Main Authors: Minh, Tam Tran Thi, Hikichi, Yuta, Miki, Shoji, Imanari, Yuriko, Kusagawa, Shigeru, Okazaki, Midori, Thu, Thao Dang Thi, Shiino, Teiichiro, Matsuoka, Saori, Yamamoto, Hiroyuki, Ohashi, Jun, Hall, William W., Matano, Tetsuro, Thi, Lan Anh Nguyen, Kawana-Tachikawa, Ai
• Format: Article
• Language: English
• Subjects: CD8-Positive T-Lymphocytes; Cohort Studies; Epitopes; Escape mutation, Viral fitness; HIV Infections; HIV Seropositivity; Human Immunodeficiency Virus type-1; Human Leukocyte Antigen; Humans; Vietnam
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2022.12.016

•The protective effect of HLA-B*57:01/58:01 on HIV-1 CRF01_AE infection was examined.•The protective impact is impaired against CRF01_AE infection.•TW10-specific CD8+ T cells select for T242N even in CRF01_AE with viral fitness cost.•Less non-TW10 epitope presentation may contribute to the impaired protective impact. Human Leukocyte Antigen HLA-B*57:01 and B*58:01 are considered anti-HIV-1 protective alleles. HLA-B*57:01/58:01-restricted HIV-1 Gag TW10 (TSTLQEQIGW, Gag residues 240-249) epitope-specific CD8+ T cell responses that frequently select for a Gag escape mutation, T242N, with viral fitness cost are crucial for HIV-1 control. Although this finding has been observed in cohorts where HIV-1 subtype B or C predominates, the protective impact of HLA-B*57:01/58:01 has not been reported in Southeast Asian countries where HIV-1 CRF01_AE is the major circulating strain. Here, the effect of HLA-B*57:01/58:01 on CRF01_AE infection was investigated. The correlation of HLA-B*57:01/58:01 with viral load and CD4 counts were analyzed in the CRF01_AE-infected Vietnamese cohort (N = 280). The impact of the T242N mutation on CRF01_AE replication capacity was assessed. HLA-B*57:01/58:01-positive individuals mostly had HIV-1 with T242N (62/63) but showed neither a significant reduction in viral load nor increased CD4 counts relative to B*57:01/58:01-negative participants. In vitro and in vivo analyses revealed a significant reduction in viral fitness of CRF01_AE with T242N. In silico analysis indicated reduced presentation of epitopes in the context of CRF01_AE compared to subtype B or C in 10/16 HLA-B*57:01/58:01-restricted HIV-1 epitopes. The protective impact of HLA-B*57:01/58:01 on CRF01_AE infection is impaired despite strong suppressive pressure by TW10-specific CD8+ T cells.