CD8+ T cell-based strong selective pressure on multiple simian immunodeficiency virus targets in macaques possessing a protective MHC class I haplotype
CD8+ T cell-based strong selective pressure on multiple simian immunodeficiency virus targets in macaques possessing a protective MHC class I haplotype
复制标题
基于 CD8 T 细胞的对具有保护性 MHC I 类单倍型的猕猴中多个猿猴免疫缺陷病毒靶标的强选择压力
DOI：
10.1016/j.bbrc.2019.03.003
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发表时间：
2019
影响因子：
3.1
通讯作者：
Yamamoto Hiroyuki
中科院分区：
文献类型：
--
作者：
Hau Trang Thi Thu;Nakamura-Hoshi Midori;Kanno Yoshiaki;Nomura Takushi;Nishizawa Masako;Seki Sayuri;Ishii Hiroshi;Kawana-Tachikawa Ai;Hall William W.;Nguyen Thi Lan Anh;Matano Tetsuro;Yamamoto Hiroyuki
在人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）感染中，宿主主要组织相容性复合物I类（MHC-I）基因型对病毒复制有很大影响，MHC-I相关的病毒基因组突变是在CD8+T细胞压力下选择的。 MHC-I 基因型与 HIV/SIV 控制的关联已在 MHC-I 等位基因水平上进行了研究，但在单倍型水平上尚未完全研究。我们之前建立了共享单个 MHC-I 单倍型的恒河猴群体。在本研究中，我们比较了具有保护性 MHC-I 单倍型 90-010-Id 的猕猴与具有非保护性 MHC-I 单倍型 90-010-Ie 的猕猴感染 SIV 后的病毒基因组多样性。这两种 MHC-I 单倍型与针对病毒 Nef 抗原相似区域的免疫显性 CD8+T 细胞反应相关。对病毒基因组序列和抗原特异性 T 细胞反应的分析显示，除了 Nef 靶标外，还有四种和两种候选病毒 CD8+T 细胞靶标分别与 90-010-Id 和 90-010-Ie 相关。在这些 CD8+T 细胞靶区域中，在具有 90-010-Id 的猕猴中，在 SIV 感染后的设定点检测到的突变数量高于具有 90-010-Ie 的猕猴。这些结果表明与保护性 MHC-I 单倍型相关的总体 CD8+T 细胞靶点具有较高的选择性压力，表明通过多个靶点特异性 CD8+T 细胞反应控制 HIV/SIV 的模式。
In human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections, host major histocompatibility complex class I (MHC-I) genotypes have a great impact on viral replication and MHC-I-associated viral genome mutations are selected under CD8+T-cell pressure. Association of MHC-I genotypes with HIV/SIV control has been investigated at MHC-I allele levels but not fully at haplotype levels. We previously established groups of rhesus macaques sharing individual MHC-I haplotypes. In the present study, we compared viral genome diversification after SIV infection in macaques possessing a protective MHC-I haplotype,90-010-Id, with those possessing a non-protective MHC-I haplotype,90-010-Ie. These two MHC-I haplotypes are associated with immunodominant CD8+T-cell responses targeting similar regions of viral Nef antigen. Analyses of viral genome sequences and antigen-specific T-cell responses showed four and two candidates of viral CD8+T-cell targets associated with90-010-Idand90-010-Ie, respectively, in addition to the Nef targets. In these CD8+T-cell target regions, higher numbers of mutations were detected at the setpoint after SIV infection in macaques possessing90-010-Idthan those possessing90-010-Ie. These results indicate higher selective pressure on overall CD8+T-cell targets associated with the protective MHC-I haplotype, suggesting a pattern of HIV/SIV control by multiple target-specific CD8+T-cell responses.