Kuznetsova A I, Gromov K B, Kireev D E, Shlykova A V, Lopatukhin A E, Kazennova E V, Lebedev A V, Tumanov A S, Kim K V, Bobkova M R
D.I. Ivanovsky Institute of Virology FSBI «National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya» of the Ministry of Health of Russia.
D.I. Ivanovsky Institute of Virology FSBI «National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya» of the Ministry of Health of Russia; FSBI «Central Research Institute for Epidemiology» of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare (Rospotrebnadzor).
Vopr Virusol. 2022 Jan 8;66(6):452-464. doi: 10.36233/0507-4088-83.
Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. Tat is characterized by high variability, with some amino acid substitutions, including subtypespecific ones, being able to influence on its functionality. HIV type 1 (HIV-1) sub-subtype A6 is the most widespread in Russia. Previous studies of the polymorphisms in structural regions of the A6 variant have shown numerous characteristic features; however, Tat polymorphism in A6 has not been studied.Goals and tasks. The main goal of the work was to analyze the characteristics of Tat protein in HIV-1 A6 variant, that is, to identify substitutions characteristic for A6 and A1 variants, as well as to compare the frequency of mutations in functionally significant domains in sub-subtype A6 and subtype B.
The nucleotide sequences of HIV-1 sub-subtypes A6, A1, A2, A3, A4, subtype B and the reference nucleotide sequence were obtained from the Los Alamos international database.
Q54H and Q60H were identified as characteristic substitutions. Essential differences in natural polymorphisms between sub-subtypes A6 and A1 have been demonstrated. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B.
Tat protein of sub-subtype A6 have some characteristics that make it possible to reliably distinguish it from other HIV-1 variants. Mutations identified in the CPP region could potentially alter the activity of Tat. The data obtained could form the basis for the drugs and vaccines development.
Tat蛋白是人类免疫缺陷病毒（HIV）转录调控的主要因子，且具有其他活性。Tat的特点是高度可变，一些氨基酸取代，包括亚型特异性取代，能够影响其功能。1型HIV（HIV-1）A6亚亚型在俄罗斯最为普遍。此前对A6变体结构区域多态性的研究已显示出许多特征；然而，A6中Tat多态性尚未得到研究。目标和任务。这项工作的主要目标是分析HIV-1 A6变体中Tat蛋白的特征，即确定A6和A1变体特有的取代，并比较A6亚亚型和B亚型功能重要结构域中的突变频率。
HIV-1 A6、A1、A2、A3、A4亚亚型、B亚型的核苷酸序列以及参考核苷酸序列均从洛斯阿拉莫斯国际数据库获得。
确定Q54H和Q60H为特征性取代。已证明A6和A1亚亚型之间自然多态性存在本质差异。在细胞穿透肽（CPP）区域，检测到一些突变（R53K、Q54H、Q54P、R57G），这些突变在A6亚亚型中比在B亚型中更常见。
A6亚亚型的Tat蛋白具有一些特征，使其能够可靠地与其他HIV-1变体区分开来。在CPP区域鉴定出的突变可能会改变Tat的活性。所获得的数据可为药物和疫苗的开发奠定基础。
