Gamaleya National Research Center for Epidemiology and Microbiology, 123098 Moscow, Russia.
Mechnikov Scientific Research Institute of Vaccines and Serums, 105064 Moscow, Russia.
Viruses. 2024 May 10;16(5):759. doi: 10.3390/v16050759.
The HIV-1 Rev protein expressed in the early stage of virus replication is involved in the nuclear export of some forms of virus RNA. Naturally occurring polymorphisms in the Rev protein could influence its activity. The association between the genetic features of different virus variants and HIV infection pathogenesis has been discussed for many years. In this study, Rev diversity among HIV-1 group M clades was analyzed to note the signatures that could influence Rev activity and, subsequently, clinical characteristics. From the Los Alamos HIV Sequence Database, 4962 Rev sequences were downloaded and 26 clades in HIV-1 group M were analyzed for amino acid changes, conservation in consensus sequences, and the presence of clade-specific amino acid substitutions (CSSs) and the Wu-Kabat protein variability coefficient (WK). Subtypes G, CRF 02_AG, B, and A1 showed the largest amino acid changes and diversity. The mean conservation of the Rev protein was 80.8%. In consensus sequences, signatures that could influence Rev activity were detected. In 15 out of 26 consensus sequences, an insertion associated with the reduced export activity of the Rev protein, 95QSQGTET96, was identified. A total of 32 CSSs were found in 16 clades, wherein A6 had the 41Q substitution in the functionally significant region of Rev. The high values of WK coefficient in sites 51 and 82, located on the Rev interaction surface, indicate the susceptibility of these positions to evolutionary replacements. Thus, the noted signatures require further investigation.
在病毒复制的早期阶段表达的 HIV-1 Rev 蛋白参与了某些形式的病毒 RNA 的核输出。Rev 蛋白中的天然存在的多态性可能会影响其活性。不同病毒变异体的遗传特征与 HIV 感染发病机制之间的关联已被讨论多年。在这项研究中，分析了 HIV-1 组 M 分支中的 Rev 多样性，以注意可能影响 Rev 活性并随后影响临床特征的特征。从洛斯阿拉莫斯 HIV 序列数据库中下载了 4962 个 Rev 序列，并分析了 HIV-1 组 M 中的 26 个分支，以研究氨基酸变化、保守共识序列以及分支特异性氨基酸取代（CSSs）和 Wu-Kabat 蛋白变异性系数（WK）的存在。G、CRF 02_AG、B 和 A1 亚型显示出最大的氨基酸变化和多样性。Rev 蛋白的平均保守率为 80.8%。在共识序列中检测到可能影响 Rev 活性的特征。在 26 个共识序列中的 15 个中，鉴定到与 Rev 蛋白出口活性降低相关的插入 95QSQGTET96。在 16 个分支中发现了总共 32 个 CSSs，其中 A6 在 Rev 功能重要区域具有 41Q 取代。位于 Rev 相互作用表面上的 51 位和 82 位位点的 WK 系数值较高，表明这些位置容易发生进化替换。因此，需要进一步研究这些特征。
