Impact of Human Leukocyte Antigen-Associated Polymorphisms on Variability of HIV-1 Accessory and Regulatory Proteins
Impact of Human Leukocyte Antigen-Associated Polymorphisms on Variability of HIV-1 Accessory and Regulatory Proteins
复制标题
人类白细胞抗原相关多态性对 HIV-1 辅助蛋白和调节蛋白变异性的影响
DOI：
10.1089/aid.2021.0055
复制
发表时间：
2021
影响因子：
1.5
通讯作者：
Ueno Takamasa
中科院分区：
文献类型：
--
作者：
Kamori Doreen;Hasan Zafrul;Carlson Jonathan;Kawana-Tachikawa Ai;Gatanaga Hiroyuki;Oka Shinichi;Ueno Takamasa
HIV-1通过获得不同影响感染过程的突变而逃逸。与HIV-1的结构蛋白和酶蛋白不同，宿主免疫介导的选择压力在多大程度上影响了辅助蛋白（Vif、Vpu、Vpr和Nef）和调节蛋白（达特和Rev）的变异性，这一点仍然是难以捉摸的。为了解决这个问题，我们分析了编码辅助和调节蛋白的病毒序列，来自446名日本人白细胞抗原（HLA）分型、慢性HIV-1亚型B感染和未接受过治疗的个体。我们观察到Vpu和Vpr是最多和最少的多态性蛋白质，平均Shannon熵分数分别为0.63和0.38。系统发生学校正的方法确定了共161个HLA相关的多态性，其中Nef和Vpu具有最高（26.6%）和最低（1.2%）的比例与HLA I类等位基因相关的氨基酸位点，分别。这些结果增加了进一步了解HLA介导的选择压力对HIV-1辅助和调节蛋白的HIV-1序列多态性的作用。
HIV-1 escapes by acquiring mutations that differentially influence the course of infection. Unlike HIV-1 structural and enzymatic proteins, it remains elusive what extent the host immune-mediated selection pressure influences the variability of the accessory (Vif, Vpu, Vpr, and Nef) and regulatory (Tat and Rev) proteins. To address this, we analyzed the viral sequences encoding accessory and regulatory proteins from 446 human leukocyte antigen (HLA)-typed, chronically HIV-1 subtype B-infected, and treatment-naive individuals in Japan. We observed that Vpu and Vpr were the most and least polymorphic proteins with the average Shannon entropy scores of 0.63 and 0.38, respectively. Phylogenetically corrected methods identified a total of 161 HLA-associated polymorphisms; whereby Nef and Vpu had the highest (26.6%) and lowest (1.2%) proportion of amino acid sites associated with HLA-class I alleles, respectively. These results add further insight on the role of HLA-mediated selection pressure on HIV-1 sequence polymorphisms of HIV-1 accessory and regulatory proteins.