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[俄罗斯联邦流行的人类免疫缺陷病毒1型(HIV-1)变体中衣壳蛋白(p24)的遗传多样性]

[Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation].

作者信息

Kuznetsova A I, Munchak I M, Lebedev A V, Tumanov A S, Kim K V, Antonova A A, Ozhmegova E N, Pronin A Y, Drobyshevskaya E V, Kazennova E V, Bobkova M R

机构信息

D.I. Ivanovsky Institute of Virology of FSBI "National Reseach Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya".

Moscow Regional Center for the Prevention and Control of AIDS and Infectious Diseases.

出版信息

Vopr Virusol. 2023 Mar 11;68(1):66-78. doi: 10.36233/0507-4088-161.

Abstract

INTRODUCTION

The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted. The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors.

MATERIALS AND METHODS

The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients.

RESULTS AND DISCUSSION

The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely.

CONCLUSION

Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

摘要

引言

人类免疫缺陷病毒(HIV)蛋白p24在病毒生命周期中发挥重要作用,也是诊断测试以及新型抗逆转录病毒药物和治疗性疫苗的靶点。世界上研究最多的HIV-1变体是B亚型。在俄罗斯,最常见的变体是A6,同时观察到重组形式(CRF63_02A6、CRF03_A6B)的传播以及G和CRF02_AG变体的流行。然而,尚未对这些变体中的p24蛋白进行详细研究。目的是研究在俄罗斯流行的HIV-1变体中p24蛋白的特征,并估计与对衣壳抑制剂类中的第一种抗逆转录病毒药物莱纳卡韦耐药相关的预先存在突变的发生频率。

材料与方法

研究对象是从洛斯阿拉莫斯国际数据库获得的核苷酸序列以及HIV感染患者的临床样本。

结果与讨论

已确定在俄罗斯流行的HIV-1变体的特征。V86A、H87Q、I91F是A6基因组中的特征性替换。结果表明,不太可能存在与对莱纳卡韦耐药相关的预先存在的突变。

结论

在俄罗斯流行的HIV-1变体中p24蛋白的特征使其能够与其他变体以及它们自身之间区分开来。在俄罗斯使用莱纳卡韦的预后总体良好。所获得的结果在开发和使用抗逆转录病毒药物及治疗性疫苗时可予以考虑。

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