Vopr Virusol. 2025 Dec 28;70(6):518-535. doi: 10.36233/0507-4088-305.
ABSTRACT
INTRODUCTION: Nef provides high level of HIV-1 replication due to synergy of its multiple functions and is an important factor in the pathogenesis of HIV infection. Nef is considered as a target for development of therapeutic agents. Mutations of drug resistance to dolutegravir can occur in Nef protein. Natural amino acid substitutions in Nef protein have been associated with the degree of progression of HIV infection, development of neurodegenerative and cardiovascular diseases in patients. The aim of the study is to investigate Nef genetic diversity in HIV-1 variants circulating in Russia and in Moscow region.
MATERIALS AND METHODS: Total 216 Nef sequences obtained from whole blood samples of patients and 77 sequences downloaded from the Los Alamos International Database were analyzed. Consensus sequences of Nef sub-subtype A6, subtype B, CRF02_AG, CRF63_02A6, CRF133_A6B, and the reference sequence NL4-3 were compared. Genetic diversity of Nef sub-subtype A6 (Nef-A6) in patients with different stages of the disease was assessed. The presence of dolutegravir-associated drug resistance mutations in the Nef protein in HIV-1 variants circulating in Russia was also investigated.
RESULTS: Differences in the spatial structures in consensus sequences of the studied HIV-1 variants were determined. It was shown that the conservatism of Nef-A6 in groups of patients with later stages of the disease was significantly higher. No mutations of drug resistance to dolutegravir were detected.
CONCLUSION: The differences in Nef sequences of HIV-1 variants circulating in Russia could affect the functional properties of the protein and could be taken into account in creating Nef-based therapies in the future. Obtained results indicate that there is no risk of resistance to dolutegravir associated with - mutations in the Nef protein. It outlines possible directions for further research into the genetic diversity of Nef.
PMID:41570232 | DOI:10.36233/0507-4088-305