Impaired protective role of HLA-B*57:01/58:01 in HIV-1 CRF01_AE infection: a cohort study in Vietnam
Impaired protective role of HLA-B*57:01/58:01 in HIV-1 CRF01_AE infection: a cohort study in Vietnam
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HLA-B*57:01/58:01 在 HIV-1 CRF01_AE 感染中的保护作用受损：越南的一项队列研究
DOI：
10.1016/j.ijid.2022.12.016
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发表时间：
2023
影响因子：
8.4
通讯作者：
Kawana-Tachikawa Ai
中科院分区：
文献类型：
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作者：
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
目的人类白细胞抗原HLA-B *57：01和B *58：01被认为是抗HIV-1的保护性等位基因。HLA-B*57：01/58：01限制性HIV-1 Gag TW 10（TSTLQEQIGW，Gag残基240-249）表位特异性CD 8 +T细胞应答经常选择Gag逃逸突变T242 N，具有病毒适应度成本，对于HIV-1控制至关重要。尽管在HIV-1亚型B或C占优势的队列中观察到了这一发现，但在HIV-1 CRF 01_AE是主要流行毒株的东南亚国家，尚未报告HLA-B *57：01/58：01的保护作用。方法在280例越南CRF01_AE感染者中，分析HLA-B * 57：01/58：01与病毒载量和CD 4计数的相关性。结果HLA-B * 57：01/58：01阳性个体大多数携带HIV-1 T242 N（62/63），但与B *57：01/58：01阴性个体相比，病毒载量和CD 4计数均未显著降低。体外和体内分析显示，携带T242 N的CRF01_AE的病毒适合度显著降低。计算机模拟分析显示，与B或C亚型相比，在10/16 HLA-B * 57：01/58：01限制性HIV-1表位中，CRF01_AE的表位呈递减少。尽管TW 10特异性CD 8 +T细胞的强大抑制压力，但CRF01_AE感染上的01受损。
ObjectivesHuman Leukocyte AntigenHLA-B*57:01andB*58:01are 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 ofHLA-B*57:01/58:01has not been reported in Southeast Asian countries where HIV-1 CRF01_AE is the major circulating strain. Here, the effect ofHLA-B*57:01/58:01on CRF01_AE infection was investigated.MethodsThe correlation ofHLA-B*57:01/58:01with 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.ResultsHLA-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 toB*57:01/58:01-negative participants.In vitroandin vivoanalyses revealed a significant reduction in viral fitness of CRF01_AE with T242N.In silicoanalysis 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.ConclusionThe protective impact ofHLA-B*57:01/58:01on CRF01_AE infection is impaired despite strong suppressive pressure by TW10-specific CD8+T cells.