Genetic diversity of Vif protein in human immunodeficiency virus type 1 variants (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1) that circulated in the Moscow region in 2019–2020
- Authors: Antonova A.A.1, Protasova L.A.1, Kim K.V.1, Munchak I.M.1, Mezhenskaya E.N.1, Orlova-Morozova E.A.2, Pronin A.Y.2, Prilipov A.G.1, Kuznetsova A.I.1
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Affiliations:
- D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya
- Center for the Prevention and Control of AIDS and Infectious Diseases
- Issue: Vol 70, No 2 (2025)
- Pages: 117-132
- Section: ORIGINAL RESEARCH
- URL: https://ogarev-online.ru/0507-4088/article/view/310651
- DOI: https://doi.org/10.36233/0507-4088-281
- EDN: https://elibrary.ru/qoqqce
- ID: 310651
Cite item
Abstract
Introduction. The Vif protein counteracts cellular deaminases, APOBEC3, which prevent viral replication. Vif is used for development of therapeutic agents. Natural polymorphisms in Vif can affect its functionality and may be associated with accelerated progression of HIV-infection to the AIDS. The study of Vif features in HIV-1 variants circulating in Russia has not been conducted previously.
The aim of the study: to study the genetic diversity of Vif in the HIV-1 variants that circulated in the Moscow region in 2019–2020.
Materials and methods. 234 whole blood samples obtained from HIV-infected patients without experience of therapy were analyzed. The study design included the following stages: extraction of proviral DNA, amplification of the vif gene, sequencing, identification of genetic variants, followed by a study of consensus sequences of the most common genetic variants of HIV-1, analysis of the conservation and genetic diversity of Vif-A6 (Vif protein of HIV-1 sub-subtype A6 variants) in patients with different stages of the disease, and assessment of genetic diversity of Vif-A6 in the Moscow region.
Results. A high degree of genetic diversity of vif gene was revealed. Consensus sequences of Vif in B and CRF63_02A6 variants were obtained for the first time. Characteristic substitutions in the consensus sequences were determined for the most common HIV-1 variants.
Conclusion. The limitation of this study is the small sample of B and CRF63_02A6. The results obtained may be of interest and may be taken into account in the development of therapeutic agents based on the Vif protein, as well as in the study of the pathogenicity of HIV-1 sub-subtype A6.
Keywords
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##article.viewOnOriginalSite##About the authors
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, MoscowLarisa 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, MoscowKristina 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, MoscowIana 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, MoscowEkaterina 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, MoscowElena 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, Moscow region, KotelnikiAlexander 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, Moscow region, KotelnikiAlexey 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, MoscowAnna I. Kuznetsova
D.I. Ivanovsky Institute of Virology of National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya
Author for correspondence.
Email: a-myznikova@list.ru
ORCID iD: 0000-0001-5299-3081
Head of laboratory of T-lymphotropic viruses, PhD, leading researcher
Russian Federation, 123098, MoscowReferences
- Rose K.M., Marin M., Kozak S.L., Kabat D. The viral infectivity factor (Vif) of HIV-1 unveiled. Trends Mol. Med. 2004; 10(6): 291–7. https://doi.org/10.1016/j.molmed.2004.04.008
- Stupfler B., Verriez C., Gallois-Montbrun S., Marquet R., Paillart J.C. Degradation Independent inhibition of APOBEC3G by the HIV-1 Vif protein. Viruses. 2021; 13(4): 617. https://doi.org/10.3390/v13040617
- Sheehy A.M., Gaddis N.C., Choi J.D., Malim M.H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002; 418(6898): 646–50. https://doi.org/10.1038/nature00939
- Mangeat B., Turelli P., Caron G., Friedli M., Perrin L., Trono D. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003; 424(6944): 99–103. https://doi.org/10.1038/nature01709
- Hultquist J.F., Lengyel J.A., Refsland E.W., LaRue R.S., Lackey L., Brown W.L., et al. Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-Deficient HIV-1. J. Virol. 2011; 85(21): 11220–34. https://doi.org/10.1128/JVI.05238-11
- Wang X., Abudu A., Son S., Dang Y., Venta P.J., Zheng Y.H. Analysis of human APOBEC3H haplotypes and anti-human immunodeficiency virus type 1 activity. J. Virol. 2011; 85(7): 3142–52. https://doi.org/10.1128/JVI.02049-10
- Guo F., Cen S., Niu M., Yang Y., Gorelick R.J., Kleiman L. The interaction of APOBEC3G with human immunodeficiency virus type 1 nucleocapsid inhibits tRNA3Lys annealing to viral RNA. J. Virol. 2007;81(20):11322–31. https://doi.org/10.1128/JVI.00162-07
- Xu W.K., Byun H., Dudley J.P. The role of APOBECs in viral replication. Microorganisms. 2020; 8(12): 1899. https://doi.org/10.3390/microorganisms8121899
- Azimi F.C., Lee J.E. Structural perspectives on HIV-1 Vif and APOBEC3 restriction factor interactions. Protein Sci. 2020; 29(2): 391–406. https://doi.org/10.1002/pro.3729
- Friedler A., Zakai N., Karni O., Friedler D., Gilon C., Loyter A. Identification of a nuclear transport inhibitory signal (NTIS) in the basic domain of HIV-1 Vif protein. J. Mol. Biol. 1999; 289(3): 431–7. https://doi.org/10.1006/jmbi.1999.2785
- Takaori-Kondo A., Shindo K. HIV-1 Vif: a guardian of the virus that opens up a new era in the research field of restriction factors. Front. Microbiol. 2013; 4: 34. https://doi.org/10.3389/fmicb.2013.00034
- Simon V., Zennou V., Murray D., Huang Y., Ho D.D., Bieniasz P.D. Natural variation in Vif: differential impact on APOBEC3G/3F and a potential role in HIV-1 diversification. PLoS Pathog. 2005; 1(1): e6. https://doi.org/10.1371/journal.ppat.0010006
- Iwabu Y., Kinomoto M., Tatsumi M., Fujita H., Shimura M., Tanaka Y., et al. Differential anti-APOBEC3G activity of HIV-1 Vif proteins derived from different subtypes. J. Biol. Chem. 2010; 285(46): 35350–8. https://doi.org/10.1074/jbc.M110.173286
- Ronsard L., Raja R., Panwar V., Saini S., Mohankumar K., Sridharan S., et al. Genetic and functional characterization of HIV-1 Vif on APOBEC3G degradation: First report of emergence of B/C recombinants from North India. Sci. Rep. 2015; 5: 15438. https://doi.org/10.1038/srep15438
- Gromov K.B., Laga V.Y., Murzakova A.V., Kireev D.E. Analysis of polymorphism of non-structural HIV-1 Vif and Rev genes. In: Molecular Diagnostics – 2017: Proceedings of the IX All-Russian Scientific and Practical Conference with International Participation [Molekulyarnaya diagnostika – 2017: sbornik trudov IKH Vserossiiskoi nauchno-prakticheskoi konferentsii s mezhdunarodnym uchastiem]. Moscow; 2017: 455–6. (in Russian)
- De Maio F.A., Rocco C.A., Aulicino P.C., Bologna R., Mangano A., Sen L. Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms. Infect. Genet. Evol. 2011; 11(6): 1256–62. https://doi.org/10.1016/j.meegid.2011.04.020
- Bizinoto M.C., Yabe S., Leal É., Kishino H., Martins L. de O., de Lima M.L., et al. Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count. BMC Infect. Dis. 2013; 13: 173. https://doi.org/10.1186/1471-2334-13-173
- Villanova F., Barreiros M., Janini L.M., Diaz R.S., Leal É. Genetic diversity of HIV-1 gene Vif among treatment-naive Brazilians. AIDS Res. Hum. Retroviruses. 2017; 33(9): 952–9. https://doi.org/10.1089/AID.2016.0230
- Bennett R.P., Salter J.D., Smith H.C. A new class of antiretroviral enabling innate immunity by protecting APOBEC3 from HIV Vif-dependent degradation. Trends Mol. Med. 2018; 24(5): 507–20. https://doi.org/10.1016/j.molmed.2018.03.004
- Sharkey M., Sharova N., Mohammed I., Huff S.E., Kummetha I.R., Singh G., et al. HIV-1 escape from small-molecule antagonism of Vif. mBio. 2019; 10(1): e00144-19. https://doi.org/10.1128/mBio.00144-19
- Duan S., Wang S., Song Y., Gao N., Meng L., Gai Y., et al. A novel HIV-1 inhibitor that blocks viral replication and rescues APOBEC3s by interrupting Vif/CBFβ interaction. J. Biol. Chem. 2020; 295(43): 14592–605. https://doi.org/10.1074/jbc.RA120.013404
- Akbari E., Seyedinkhorasani M., Bolhassani A. Conserved multiepitope vaccine constructs: A potent HIV-1 therapeutic vaccine in clinical trials. Braz. J. Infect. Dis. 2023; 27(3): 102774. https://doi.org/10.1016/j.bjid.2023.102774
- Guerra-Palomares S.E., Hernandez-Sanchez P.G., Esparza-Perez M.A., Arguello J.R., Noyola D.E., Garcia-Sepulveda C.A. Molecular characterization of Mexican HIV-1 Vif sequences. AIDS Res. Hum. Retroviruses. 2016; 32(3): 290–5. https://doi.org/10.1089/AID.2015.0290
- Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide. Curr. Opin. HIV AIDS. 2019; 14(3): 153–60. https://doi.org/10.1097/COH.0000000000000534
- Williams M.E. HIV-1 Vif protein sequence variations in South African people living with HIV and their influence on Vif-APOBEC3G interaction. Eur. J. Clin. Microbiol. Infect. Dis. 2024; 43(2): 325–38. https://doi.org/10.1007/s10096-023-04728-0
- Antonova A.A., Kuznetsova A.I., Ozhmegova E.N., Lebedev A.V., Kazennova E.V., Kim K.V., et al. Genetic diversity of HIV-1 at the current stage of the epidemic in the Russian Federation: an increase in the prevalence of recombinant forms. VICH-infektsiya i immunosupressii. 2023; 15(3): 61–72. https://doi.org/10.22328/2077-9828-2023-15-3-61-72 https://elibrary.ru/tpwttn (in Russian)
- Kuznetsova A.I., Gromov K.B., Kireev D.E., Shlykova A.V., Lopatukhin A.E., Kazennova E.V., et al. Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1). Voprosy virusologii. 2021; 66(6): 452–63. https://doi.org/10.36233/0507-4088-83 https://elibrary.ru/cmzgyc (in Russian)
- Kuznetsova A., Kim K., Tumanov A., Munchak I., Antonova A., Lebedev A., et al. Features of Tat protein in HIV-1 sub-subtype A6 variants circulating in the Moscow Region, Russia. Viruses. 2023; 15(11): 2212. https://doi.org/10.3390/v15112212 https://elibrary.ru/ucqyal
- Antonova A.A., Lebedev A.V., Kazennova E.V., Kim K.V., Ozhmegova E.N., Tumanov A.S., et al. Variability of VPU protein in HIV-1 sub-subtype A6 in patients with different stages of HIV infection. VICH-infektsiya i immunosupressii. 2024; 16(2): 40–50. https://doi.org/10.22328/2077-9828-2024-16-2-40-50 https://elibrary.ru/lpjxqk (in Russian)
- Lebedev A., Kim K., Ozhmegova E., Antonova A., Kazennova E., Tumanov A., et al. Rev protein diversity in HIV-1 group M clades. Viruses. 2024; 16(5): 759. https://doi.org/10.3390/v16050759
- Antonova A.A., Lebedev A.V., Ozhmegova E.N., Shlykova A.V., Lapavok I.A., Kuznetsova A.I. Variability of non-structural proteins in HIV-1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1, sub-subtype A6) variants circulating in different regions of the Russian Federation. Voprosy virusologii. 2024; 69(5): 470–80. https://doi.org/10.36233/0507-4088-262 https://elibrary.ru/wbbkuq (in Russian)
- Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic. Acids. Res. 1988; 16(3): 1215. https://doi.org/10.1093/nar/16.3.1
- Larsson A. AliView: a fast and lightweight alignment viewer and editor for large datasets. Bioinformatics. 2014; 30(22): 3276–8. https://doi.org/10.1093/bioinformatics/btu531
- Struck D., Lawyer G., Ternes A.M., Schmit J.C., Bercoff D.P. COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification. Nucleic Acids Res. 2014; 42(18): e144. https://doi.org/10.1093/nar/gku739
- Schultz A.K., Bulla I., Abdou-Chekaraou M., Gordien E., Morgenstern B., Zoaulim F., et al. jpHMM: recombination analysis in viruses with circular genomes such as the hepatitis B virus. Nucleic Acids Res. 2012; 40: W193-8. https://doi.org/10.1093/nar/gks414.
- Nguyen L.T., Schmidt H.A., von Haeseler A., Minh B.Q. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 2015; 32(1): 268–74. https://doi.org/10.1093/molbev/msu300
- Darriba D., Taboada G.L., Doallo R., Posada D. jModelTest 2: more models, new heuristics and parallel computing. Nat Methods. 2012; 9(8): 772. https://doi.org/10.1038/nmeth.2109.
- Letunic I., Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 2021; 49(W1): W293–6. https://doi.org/10.1093/nar/gkab301
- Berezov T.T., Korovkin B.F. Biological Chemistry [Biologicheskaya khimiya]. Moscow: Meditsina; 1998 (in Russian)
- Lobanov M.Y., Pereyaslavets L.B., Likhachev I.V., Matkarimov B.T., Galzitskaya O.V. Is there an advantageous arrangement of aromatic residues in proteins? Statistical analysis of aromatic interactions in globular proteins. Comput. Struct. Biotechnol. J. 2021; 19: 5960–8. https://doi.org/10.1016/j.csbj.2021.10.036
- Duan S., Wang S., Song Y., Gao N., Meng L., Gai Y., et al. A novel HIV-1 inhibitor that blocks viral replication and rescues APOBEC3s by interrupting vif/CBFβ interaction. J. Biol. Chem. 2020; 295(43): 14592–605. https://doi.org/10.1074/jbc.RA120.013404
- Kardani K., Hashemi A., Bolhassani A. Comparison of HIV-1 Vif and Vpu accessory proteins for delivery of polyepitope constructs harboring Nef, Gp160 and P24 using various cell penetrating peptides. PLoS One. 2019; 14(10): e0223844. https://doi.org/10.1371/journal.pone.0223844
- Delviks-Frankenberry K.A., Ackerman D., Timberlake N.D., Hamscher M., Nikolaitchik O.A., Hu W.S., et al. Development of Lentiviral Vectors for HIV-1 Gene Therapy with Vif-Resistant APOBEC3G. Mol. Ther. Nucleic Acids. 2019; 18: 1023–38. https://doi.org/10.1016/j.omtn.2019.10.024
- Murzakova A., Kireev D., Baryshev P., Lopatukhin A., Serova E., Shemshura A., et al. Molecular epidemiology of HIV-1 subtype G in the Russian Federation. Viruses. 2019; 11(4): 348. https://doi.org/10.3390/v11040348
- Bobkova M.R. Defective HIV proviruses: possible involvement in the HIV infection pathogenesis. Voprosy virusulogii. 2024; 69(5): 399–414. https://doi.org/10.36233/0507-4088-261 https://elibrary.ru/pselci (in Russian)
- Veselova E.I., Kaminskiy G.D., Samoylova A.G., Vasilyeva I.A. HIV reservoir in HIV patients. Tuberkulez i bolezni legkikh. 2019; 97(5): 50–7. http://doi.org/10.21292/2075-1230-2019-97-5-50-57 https://elibrary.ru/hfadpt (in Russian)
- Jayaraman B., Fernandes J.D., Yang S., Smith C., Frankel A.D. Highly mutable linker regions regulate HIV-1 rev function and stability. Sci. Rep. 2019; 9(1): 5139. https://doi.org/10.1038/s41598-019-41582-7
- Li L., Dahiya S., Kortagere S., Aiamkitsumrit B., Cunningham D., Pirrone V., et al. Impact of Tat genetic variation on HIV-1 disease. Adv. Virol. 2012; 2012: 123605. https://doi.org/10.1155/2012/123605
- Chen G., He Z., Wang T., Xu R., Yu X.F. A patch of positively charged amino acids surrounding the human immunodeficiency virus type 1 Vif SLVx4Yx9Y motif influences its interaction with APOBEC3G. J. Virol. 2009; 83(17): 8674–82. https://doi.org/10.1128/JVI.00653-09
- Williams ME. HIV-1 Vif protein sequence variations in South African people living with HIV and their influence on Vif-APOBEC3G interaction. Eur. J. Clin. Microbiol. Infect. Dis. 2024; 43(2): 325–38. https://doi.org/10.1007/s10096-023-04728-0
- Savchenko-Belsky V., Maltseva M., Maslova A. Problems and prospects of the development of the transport system of the Moscow agglomeration. Transportnoe delo Rossii. 2022; (1): 124–7. https://doi.org/10.52375/20728689_2022_1_124 https://elibrary.ru/cctqsp (in Russian)
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