# Genetic Diversity of Vif and Vpr Accessory Proteins in HIV-1 Group M Clades

## TL;DR

This study examines the genetic diversity of HIV-1 Vif and Vpr proteins across different clades to identify variations that may impact disease progression and drug development.

## Contribution

The study identifies clade-specific amino acid substitutions in Vif and Vpr and shows for the first time that Vif can interact with APOBEC3G as an oligomer.

## Key findings

- The average conservation degree in HIV-1 group M was 86.4% for Vif and 91.3% for Vpr.
- Sub-subtype A6 showed the lowest amino acid diversity, while subtype B showed the highest.
- Clade-specific substitutions in Vif and Vpr were identified that may influence pathogenesis.

## Abstract

Vif and Vpr are HIV-1 accessory proteins that create optimal conditions for viral replication. They are considered as potential targets for the development of therapeutic agents. Natural amino acid substitutions in these proteins have previously been associated with disease progression. The aim of this study was to analyze the genetic diversity of Vif and Vpr in HIV-1 group M clades. A total of 5286 sequences were downloaded and analyzed. For 37 clades in group M, the consensus sequences, amino acid natural variation, and clade-specific amino acid residue substitutions (CSSs) were evaluated. Structural analysis and modeling of consensus sequences were performed for subtypes A1, B, C, and D. The average conservation degree in the HIV-1 group M was 86.4% for Vif and 91.3% for Vpr. In both proteins, the lowest amino acid diversity was observed in sub-subtype A6, and the highest in subtype B. In consensus sequences, the substitutions, which might influence pathogenesis, have been determined: in Vif—22H (11_cpx, 91_cpx) and 136P (A6, 01_AE, 15_01B, 59_01B, 89_BF1, 103_01B, 111_01C, 133_A6B), in Vpr—41N (06_cpx) and 55A (B, 07_BC, 35_01D, 56_cpx, 66_cpx, 66_BF1, 71_BF1, 85_BC, 137_0107). In functional motifs, CSSs associated with changes in the chemical properties of amino acid residues were noted. These findings could be taken into account for the development of therapeutic drugs in the future. No correlation was observed between the subtypes and the spatial organization of the oligomeric structures of Vif and Vpr. Using the structural analysis and modeling, it has been shown for the first time that Vif can interact with APOBEC3G as an oligomer.