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1.
Vopr Virusol ; 66(6): 452-464, 2022 01 08.
Article in Russian | MEDLINE | ID: mdl-35019252

ABSTRACT

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS AND DISCUSSION: 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. CONCLUSION: 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.


Subject(s)
HIV-1 , tat Gene Products, Human Immunodeficiency Virus , HIV Infections , HIV-1/genetics , Humans , Mutation , tat Gene Products, Human Immunodeficiency Virus/genetics
2.
Vopr Virusol ; 64(6): 281-290, 2019.
Article in Russian | MEDLINE | ID: mdl-32168442

ABSTRACT

INTRODUCTION: 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. OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS AND DISCUSSION: 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. CONCLUSION: Characteristic substitutions were found in the Nef structure, potentially capable of weakening the replicative properties of HIV-1 variant A6.


Subject(s)
Amino Acid Substitution , HIV Infections/epidemiology , HIV-1/genetics , Polymorphism, Genetic , nef Gene Products, Human Immunodeficiency Virus/genetics , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , Commonwealth of Independent States/epidemiology , Gene Expression , HIV Infections/immunology , HIV Infections/virology , HIV-1/classification , HIV-1/immunology , High-Throughput Nucleotide Sequencing , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Phylogeny , Virus Replication/immunology , nef Gene Products, Human Immunodeficiency Virus/metabolism
3.
Vopr Virusol ; 62(4): 154-161, 2017.
Article in Russian | MEDLINE | ID: mdl-29733164

ABSTRACT

The results of the molecular-epidemiological analysis of HIV-1 variants circulating in Arkhangelsk and Murmansk - northern seaports of Russia - were presented. In these seaports the HIV-1 variants belonging to subtype A1 were predominant (93% in Murmansk, 83% in Arkhangelsk). In addition to these variants, viruses of other subtypes such as B, C, D and recombinant forms CRF02_AG and CRF03_AB were identifed. The heterogeneity of circulating HIV-1 variants was higher in Arkhangelsk than in Murmansk. According to the results of phylogenetic analysis, subtype A1 sequences formed the common branch with nucleotide sequences of IDU-A strains found in other regions of Russia. HIV-1 variants of subtype B sub-clustered with sequences of East European B-variants. The recombinant strains CRF02_AG formed the common branch with HIV-1 sequences from Central Asia republics of the former USSR. Among 124 therapy-naive patients from Arkhangelsk and Murmansk (n = 124) the transmitted resistance was less than 5%.


Subject(s)
HIV Infections/epidemiology , HIV-1/genetics , HIV Infections/virology , Humans , Phylogeny , Russia
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