Nef HIV-1 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1), multifunctional protein: features of genetic virus variants circulating in Russia

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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.

About the authors

Anna I. Kuznetsova

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: a-myznikova@list.ru
ORCID iD: 0000-0001-5299-3081

head of laboratory of T-lymphotropic viruses, PhD, leading researcher

Russian Federation, 123098, Moscow

Anastasiia A. Antonova

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: anastaseika95@mail.ru
ORCID iD: 0000-0002-9180-9846

PhD, Researcher, Laboratory of T-lymphotropic viruses

Russian Federation, 123098, Moscow

Larisa A. Protasova

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: larisa.protasova.03@mail.ru
ORCID iD: 0009-0001-0430-1578

research assistant, Laboratory of T-lymphotropic viruses

Russian Federation, 123098, Moscow

Anna V. Glyakina

Institute of Mathematical Problems of Biology RAS – the Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences

Email: quark777a@gmail.com
ORCID iD: 0000-0002-6352-2880

PhD, Researcher

Russian Federation, 142290, Pushchino

Kristina V. Kim

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: kimsya99@gmail.com
ORCID iD: 0000-0002-4150-2280

junior researcher, Laboratory of T-lymphotropic viruses

Russian Federation, 123098, Moscow

Iana M. Munchak

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: yana_munchak@mail.ru
ORCID iD: 0000-0002-4792-8928

junior researcher, Laboratory of T-lymphotropic viruses

Russian Federation, 123098, Moscow

Ekaterina N. Mezhenskaya

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: belokopytova.01@mail.ru
ORCID iD: 0000-0002-3110-0843

PhD, Researcher, Laboratory of T-lymphotropic viruses

Russian Federation, 123098, Moscow

Elena A. Orlova-Morozova

Center for the Prevention and Control of AIDS and Infectious Diseases

Email: orlovamorozova@gmail.com
ORCID iD: 0000-0003-2495-6501

PhD, Head of outpatient department

Russian Federation, 140053, Kotelniki

Alexander Yu. Pronin

Center for the Prevention and Control of AIDS and Infectious Diseases

Email: alexanderp909@gmail.com
ORCID iD: 0000-0001-9268-4929

PhD, Chief Physician

Russian Federation, 140053, Kotelniki

Alexey G. Prilipov

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: a_prilipov@mail.ru
ORCID iD: 0000-0001-8755-1419

Doctor of Biological Sciences, leading researcher, head of the laboratory of molecular genetics

Russian Federation, 123098, Moscow

Oxana V. Galzitskaya

D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya; Institute of Theoretical and Experimental Biophysics RAS

Author for correspondence.
Email: ogalzit@vega.protres.ru
ORCID iD: 0000-0002-3962-1520

Doctor of Physical and Mathematical Sciences, Head of the Bioinformatics Laboratory, Chief Researcher

Russian Federation, 123098, Moscow; 142290, Pushchino

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