HLA-B*35:05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B*57 frequency is low
HLA-B*35:05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B*57 frequency is low
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DOI：
10.1097/qad.0000000000000206
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发表时间：
2014-04-24
期刊：
影响因子：
3.8
通讯作者：
Sawanpanyalert, Pathom
中科院分区：
文献类型：
--
作者：
Mori, Masahiko;Wichukchinda, Nuanjun;Sawanpanyalert, Pathom
目的：鉴定东南亚 HIV 感染人群中的保护性人类白细胞抗原（HLA）等位基因，该人群中 HLA-B*57 患病率低于其他种族，HIV-1 CRF01_AE 是主要循环亚型。设计：泰国慢性 HIV 感染患者的横断面研究。方法：招募了 557 名 HIV-1 CRF01_AE 感染泰国人。确定他们的 HLA 类型和病毒载量，以统计分析病毒对照中每个等位基因的关联。计算机分子动力学还用于评估 HLA 结构变异对表位结合的影响。结果：HLA-B*35:05 被确定为最具保护性的等位基因（P = 0.003，q = 0.17），以及 HLA-B*57:01（P = 0.044，q = 0.31）。从结构上看，HLA-B*35:05属于HLA-B*35等位基因的HLA-B*35-PY组；然而，与在残基 97 处携带 Arg (R) 的其他 HLA-B*35 等位基因不同，它在位于肽结合沟内的 T94、L95 和 S97 处具有独特的序列。三维 HLA 结构和分子动力学分析表明，与疾病易感 HLA-B*35-PY 等位基因 HLA-B*35:01 相比，HLA-B*35:05 中的 S97 导致沟道灵活性较低，α 螺旋之间的距离较短。结论：这些数据表明 HLA-B*57 跨种族存在保护作用，并强调 HLA-B*35:05对 CRF01_AE 亚型感染的泰国人具有独特保护作用的等位基因。 HLA-B*35:05 与传统 HLA-B*35-PY 结构序列在肽结合沟处的差异与之前的研究一致，这些研究已确定 HLA 残基 97 在塑造 HLA 对 HIV 免疫控制的影响方面具有强烈影响，并且更受限制的肽结合基序可能与改善的控制有关。
Objective:To identify protective human leukocyte antigen (HLA) alleles in an HIV-infected south-east Asian population, in whom HLA-B*57 prevalence is lower than other ethnic groups, and HIV-1 CRF01_AE is the dominant circulating subtype.Design:Cross-sectional study of Thai patients with chronic HIV infection.Methods:Five hundred and fifty-seven HIV-1 CRF01_AE-infected Thais were recruited. Their HLA type and viral load were determined to statistically analyze the association of each allele in viral control. In-silico molecular dynamics was also used to evaluate the effect of HLA structure variants on epitope binding.Results:HLA-B*35:05 was identified as the most protective allele (P = 0.003, q = 0.17), along with HLA-B*57:01 (P = 0.044, q = 0.31). Structurally, HLA-B*35:05 belonged to the HLA-B*35-PY group of HLA-B*35 alleles; however, unlike the other HLA-B*35 alleles that carry Arg (R) at residue 97, it has unique sequences at T94, L95, and S97, located within the peptide-binding groove. Analysis of the three-dimensional HLA structure and molecular dynamics indicates that S97 in HLA-B*35:05 leads to less flexibility in the groove, and shorter distances between the alpha-helixes compared with the disease-susceptible HLA-B*35-PY allele, HLA-B*35:01.Conclusion:These data indicate the existence of a protective effect of HLA-B*57 across ethnic groups and highlight HLA-B*35:05 as an allele uniquely protective in subtype CRF01_AE-infected Thais. The divergence of HLA-B*35:05 from conventional HLA-B*35-PY structural sequences at the peptide-binding groove is consistent with previous studies that have identified HLA residue 97 as strongly influential in shaping HLA impact on immune control of HIV, and that a more restricted peptide-binding motif may be associated with improved control.