Gromov K B, Kazennova E V, Kireev D E, Murzakova A V, Lopatukhin A E, Bobkova M R
National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Moscow, 123098, Russia.
Central Research Institute of Epidemiology, Moscow, 111123, Russia.
Vopr Virusol. 2019;64(6):281-290. doi: 10.36233/0507-4088-2019-64-6-281-290.
The human immunodeficiency virus (HIV) Nef protein is one of the key factors determining the infectivity and replicative properties of HIV. With the ability to interact with numerous proteins of the host cell, this protein provides the maximum level of virus production and protects it from the immune system. The main activities of Nef are associated with a decrease in the expression of the CD4 receptor and major histocompatibility complex class I molecules (MHC-I), as well as the rearrangement of the cytoskeleton. These properties of the protein are determined by the structure of several motifs in the structure of the nef gene encoding it, which is quite variable.
The main goal of the work was to analyze the characteristics of Nef protein of HIV-1 variant A6, which dominates in the countries of the former USSR. The objective of the work was a comparative analysis of natural polymorphisms in the nef gene of HIV-1 sub-subtypes A6 and A1 and subtype B.
The sequences of the HIV-1 genome obtained during the previous work of the laboratory were used, as well as the reference sequence from GenBank. In this work, Sanger sequencing and new generation sequencing methods, as well as bioinformation analysis methods were used.
The existence of noticeable differences in the prevalence of Nef natural polymorphisms (A32P, E38D, I43V, A54D, Q104K, H116N, Y120F, Y143F, V168M, H192T, V194R, R35Q, D108E, Y135F, E155K, E182M, R184K and F191L), some of which are characteristic mutations for variant A6, was shown.
Characteristic substitutions were found in the Nef structure, potentially capable of weakening the replicative properties of HIV-1 variant A6.
人类免疫缺陷病毒(HIV)Nef蛋白是决定HIV感染性和复制特性的关键因素之一。该蛋白能够与宿主细胞的多种蛋白相互作用,可实现病毒的最大产量并保护其免受免疫系统攻击。Nef的主要活性与CD4受体和主要组织相容性复合体I类分子(MHC-I)表达的降低以及细胞骨架的重排有关。该蛋白的这些特性由编码它的nef基因结构中的几个基序结构决定,而该结构具有相当大的变异性。
这项工作的主要目标是分析在前苏联国家占主导地位的HIV-1 A6变异株的Nef蛋白特征。这项工作的目的是对HIV-1 A6和A1亚亚型以及B亚型nef基因中的自然多态性进行比较分析。
使用了实验室先前工作中获得的HIV-1基因组序列以及来自GenBank的参考序列。在这项工作中,采用了桑格测序法和新一代测序方法以及生物信息分析方法。
研究表明,Nef自然多态性(A32P、E38D、I43V、A54D、Q104K、H116N、Y120F、Y143F、V168M、H192T、V194R、R35Q、D108E、Y135F、E155K、E182M、R184K和F191L)的流行存在显著差异,其中一些是A6变异株的特征性突变。
在Nef结构中发现了特征性替代,可能会削弱HIV-1 A6变异株的复制特性。