Shadabi Elnaz, Liang Binhua, Plummer Frank, Luo Ma
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
JC Wilt Infectious Disease Research Centre, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Curr HIV Res. 2018;16(2):130-142. doi: 10.2174/1570162X16666180330140807.
Human immunodeficiency virus-1 (HIV-1) mutates rapidly to escape host immune pressure. This results in the generation of positively selected mutations (PSM) throughout the viral genome. Escape mutations in Nef, one of the accessory proteins of HIV-1, which plays an important role in viral pathogenicity have previously been identified in several large cohort studies, but the evolution of PSMs overtime in various HIV-1 subtypes remains unknown.
161 clade A1, 3093 clade B, 647 clade C and 115 clade D HIV-1 nef sequences were obtained from the HIV Database of Los Alamos National Laboratory and aligned using MEGA 6.0. The sequences from each clade were grouped based on the year of collection. Quasi analysis was used to identify PSMs and the number and locations of PSMs were compared among different subtypes.
PSMs for all four subtypes were distributed across the sequence of Nef, and conserved residues F90, W113, PxxPxR (a.a 72-77) remain unaltered overtime. The frequency of PSMs was stable among subtype B sequences but increased overtime for other subtypes. Phylogenetic analysis shows that sequences containing PSMs tend to cluster together at both inter and intra- subtype levels.
Identification of PSMs and their changes overtime within various subtypes of HIV-1 is important in defining global viral evolutionary patterns that can provide insights for designing therapeutic strategies.
人类免疫缺陷病毒1型（HIV-1）迅速变异以逃避宿主免疫压力。这导致在整个病毒基因组中产生正选择突变（PSM）。HIV-1的辅助蛋白之一Nef中的逃逸突变在病毒致病性中起重要作用，此前已在多项大型队列研究中得到鉴定，但不同HIV-1亚型中PSM随时间的演变仍不清楚。
从洛斯阿拉莫斯国家实验室的HIV数据库中获取161个A1亚型、3093个B亚型、647个C亚型和115个D亚型的HIV-1 nef序列，并使用MEGA 6.0进行比对。每个亚型的序列根据收集年份进行分组。采用准分析来鉴定PSM，并比较不同亚型中PSM的数量和位置。
所有四种亚型的PSM分布在Nef序列中，保守残基F90、W113、PxxPxR（第72-77位氨基酸）随时间保持不变。PSM的频率在B亚型序列中稳定，但在其他亚型中随时间增加。系统发育分析表明，含有PSM的序列在亚型间和亚型内水平上都倾向于聚集在一起。
鉴定HIV-1不同亚型中的PSM及其随时间的变化对于定义全球病毒进化模式很重要，这可为设计治疗策略提供见解。
