Abstract
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.
Highlights
Tat protein is a major factor of human immunodeficiency virus (HIV) transcription regulation and has other activities
We continue to discuss the specific characteristics of these proteins regarding HIV type 1 (HIV-1) sub-subtype A6, most prevalent in Russia [4, 5]; the Tat protein has become the focus of our studies
The aim of this work was to study specific characteristics of the HIV-1 sub-subtype A6 Tat region encoded by the first exon and required for transactivation; identification of characteristic substitutions, comparative analysis of A6 polymorphisms and those of А1, being closest to it, as well as detection of statistically significant differences in the dicysteine motif and the CPP region in sub-subtype A6 and subtype B whose biological and clinical properties are well known
Summary
Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. 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. One of the main reasons for this insistent need lies in the phenomenon of drug resistance in the human immunodeficiency virus (HIV), which limits the options for ART regimens, especially in patients having long treatment history. Another challenging task is development of effective drug combinations having a high level of safety and convenient dosage forms. We continue to discuss the specific characteristics of these proteins regarding HIV type 1 (HIV-1) sub-subtype A6, most prevalent in Russia [4, 5]; the Tat protein has become the focus of our studies
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