Vpr, accessory protein of human immunodeficiency virus type 1 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1): features of genetic variants of the virus circulating in the Moscow region in 2019–2020

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Introduction. Vpr is a multifunctional auxiliary HIV-1 protein. Oligomerisation is a prerequisite for the entry of Vpr into the virion and its subsequent participation in the early stages of HIV-infection. To date, natural amino acid substitutions in Vpr associated with disease progression were identified; the possibility of creating therapeutics based on Vpr is being considered.

The aim of the study is to investigate Vpr features in the most common genetic variants of HIV-1 circulating in the Moscow region in 2019–2020.

Materials and methods. HIV-1 samples obtained from 231 patients of the AIDS Prevention and Control Center in the period 2019–2020 were studied according to the scheme: proviral DNA extraction, amplification of the vpr gene, sequencing, and data analysis. Consensus Vpr sequences of the most common genetic variants in Russia and their spatial structures, variability of Vpr variants of HIV-1 sub-subtype A6 in patients with different stages of the disease were studied.

Results. Features of Vpr protein in different genetic variants of HIV-1 could influence the formation of their oligomeric forms. No sites with statistically significant differences in the frequency of amino acid substitutions were identified in patients with different stages of disease.

Conclusion. Vpr protein of HIV-1 genetic variants circulating in Russia may have differences in functional properties. Vpr-A6 variants had low variability in patients with different stages of the disease, and therefore Vpr-A6 can be considered as a target for the development of therapeutic agents.

作者简介

Anna Kuznetsova

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

编辑信件的主要联系方式.
Email: a-myznikova@list.ru
ORCID iD: 0000-0001-5299-3081

PhD, head of laboratory of T-lymphotropic viruses, PhD, leading researcher, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

Anastasiia Antonova

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya

Email: aantonova1792@gmail.com
ORCID iD: 0000-0002-9180-9846

PhD, Researcher, Laboratory of T-lymphotropic viruses, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

Ekaterina Makeeva

Moscow Polytechnic University

Email: makeevakaty13@gmail.com
ORCID iD: 0009-0005-7085-3361

student, Faculty of Chemical Engineering and Biotechnology

俄罗斯联邦, 107023, Moscow

Kristina Kim

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, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

Iana Munchak

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, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

Ekaterina Mezhenskaya

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, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

Elena 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

俄罗斯联邦, 140053, Kotelniki, Moscow region

Alexander 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

俄罗斯联邦, 140053, Kotelniki, Moscow region

Alexey Prilipov

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, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

Oxana Galzitskaya

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

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

Doctor of Physical and Mathematical Sciences, Head of the Bioinformatics Laboratory, Chief Researcher, Gamaleya National Research Center of Epidemiology and Microbiology, D.I. Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow; 142290, Pushchino, Moscow Region

参考

  1. Kogan M., Rappaport J. HIV-1 accessory protein Vpr: Relevance in the pathogenesis of HIV and potential for therapeutic intervention. Retrovirology. 2011; 8: 25. https://doi.org/10.1186/1742-4690-8-25
  2. Morellet N., Bouaziz S., Petitjean P., Roques B.P. NMR structure of the HIV-1 regulatory protein VPR. J. Mol. Biol. 2003; 327(1): 215–27. https://doi.org/10.1016/s0022-2836(03)00060-3
  3. Sawaya B.E., Khalili K., Gordon J., Taube R., Amini S. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J. Biol. Chem. 2000; 275(45): 35209–14. https://doi.org/10.1074/jbc.M005197200
  4. Fritz J.V., Dujardin D., Godet J., Didier P., De Mey J., Darlix J.L., et al. HIV-1 Vpr oligomerization but not that of Gag directs the interaction between VPR and GAG. J. Virol. 2010; 84(3): 1585–96. https://doi.org/10.1128/JVI.01691-09
  5. Venkatachari N.J., Walker L.A., Tastan O., Le T., Dempsey T.M., Li Y., et al. Human immunodeficiency virus type 1 Vpr: oligomerization is an essential feature for its incorporation into virus particles. Virol. J. 2010; 7: 119. https://doi.org/10.1186/1743-422X-7-119
  6. Nodder S.B., Gummuluru S. Illuminating the role of VPR in HIV infection of myeloid cells. Front. Immunol. 2019; 10: 1606. https://doi.org/10.3389/fimmu.2019.01606
  7. Vanegas-Torres C.A., Schindler M. HIV-1 Vpr functions in primary CD4+ T Cells. Viruses. 2024; 16(3): 420. https://doi.org/10.3390/ v16030420
  8. Zhang F., Bieniasz P.D. HIV-1 VPR induces cell cycle arrest and enhances viral gene expression by depleting CCDC137. Elife. 2020; 9: e55806. https://doi.org/10.7554/eLife.55806
  9. Huang C.Y., Chiang S.F., Lin T.Y., Chiou S.H., Chow K.C. HIV-1 VPR triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction. PLoS One. 2012; 7(3): e33657. https://doi.org/10.1371/journal.pone.0033657
  10. Zhao L., Wang S., Xu M., He Y., Zhang X., Xiong Y., et al. VPR counteracts the restriction of LAPTM5 to promote HIV-1 infection in macrophages. Nat. Commun. 2021; 12(1): 3691. https://doi.org/10.1038/s41467-021-24087-8
  11. Eldin P., Péron S., Galashevskaya A., Denis-Lagache N., Cogné M., Slupphaug G., et al. Impact of HIV-1 Vpr manipulation of the DNA repair enzyme UNG2 on B lymphocyte class switch recombination. J. Transl. Med. 2020; 18(1): 310. https://doi.org/10.1186/s12967-020-02478-7
  12. Casey Klockow L., Sharifi H.J., Wen X., Flagg M., Furuya A.K., Nekorchuk M., et al. The HIV-1 protein Vpr targets the endoribonuclease Dicer for proteasomal degradation to boost macrophage infection. Virology. 2013; 444(1-2): 191–202. https://doi.org/10.1016/j.virol.2013.06.010
  13. Li G., Makar T., Gerzanich V., Kalakonda S., Ivanova S., Pereira E.F.R., et al. HIV-1 VPR-induced proinflammatory response and apoptosis are mediated through the Sur1-Trpm4 channel in astrocytes. mBio. 2020; 11(6): e02939–20. https://doi.org/10.1128/mbio.02939-20
  14. Mukerjee R., Chang J.R., Del Valle L., Bagashev A., Gayed M.M., Lyde R.B., et al. Deregulation of microRNAs by HIV-1 VPR protein leads to the development of neurocognitive disorders. J. Biol. Chem. 2011; 286(40): 34976–85. https://doi.org/10.1074/jbc.M111.241547
  15. James T., Nonnemacher M.R., Wigdahl B., Krebs F.C. Defining the roles for VPR in HIV-1-associated neuropathogenesis. J. Neurovirol. 2016; 22(4): 403–15. https://doi.org/10.1007/s13365-016-0436-5
  16. Fabryova H., Strebel K. VPR and its cellular interaction partners: R we there yet? Cells. 2019; 8(11): 1310. https://doi.org/10.3390/cells8111310
  17. González M.E. The HIV-1 VPR protein: A multifaceted target for therapeutic intervention. Int. J. Mol. Sci. 2017; 18(1): 126. https://doi.org/10.3390/ijms18010126
  18. Dampier W., Antell G.C., Aiamkitsumrit B., Nonnemacher M.R., Jacobson J.M., Pirrone V., et al. Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status. J. Neurovirol. 2017; 23(1): 113–24. https://doi.org/10.1007/s13365-016-0462-3
  19. Hadi K., Walker L.A., Guha D., Murali R., Watkins S.C., Tarwater P., et al. Human immunodeficiency virus type 1 VPR polymorphisms associated with progressor and non-progressor individuals alter VPR-associated functions. J. Gen. Virol. 2014; 95(3): 700–11. https://doi.org/10.1099/vir.0.059576-0
  20. Colle J.H., Rose T., Rouzioux Ch., Garcia A. Two highly variable Vpr84 and Vpr85 residues within the HIV-1-Vpr C-terminal protein transduction domain control transductionnal activity and define a clade specific polymorphism. World Journal of AIDS. 2014; (4): 148–55. https://doi.org/10.4236/wja.2014.4201
  21. Hagiwara K., Ishii H., Murakami T., Takeshima S.N., Chutiwitoonchai N., Kodama E.N., et al. Synthesis of a VPR-binding derivative for use as a novel HIV-1 inhibitor. PLoS One. 2015; 10(12): e0145573. https://doi.org/10.1371/journal.pone.0145573
  22. Milani A., Baesi K., Agi E., Marouf G., Ahmadi M., Bolhassani A. HIV-1 accessory proteins: which one is potentially effective in diagnosis and vaccine development? Protein Pept. Lett. 2021; 28(6): 687–98. https://doi.org/10.2174/0929866528999201231213610
  23. 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
  24. 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)
  25. Antonova A., Kazennova E., Lebedev A., Ozhmegova E., Kuznetsova A., Tumanov A., et al. Recombinant forms of HIV-1 in the last decade of the epidemic in the Russian Federation. Viruses. 2023; 15(12): 2312. https://doi.org/10.3390/v15122312
  26. Maksimenko L.V., Sivay M.V., Totmenin A.V., Shvalov A.N., Skudarnov S.E., Ostapova T.S., et al. Novel HIV-1 A6/B recombinant forms (CRF133_A6B and URF_A6/B) circulating in Krasnoyarsk region, Russia. J. Infect. 2022; 85(6): 702–69. https://doi.org/10.1016/j.jinf.2022.10.001
  27. Halikov M.R., Ekushov V.E., Totmenin A.V., Gashnikova N.M., Antonets M.E., Tregubchak T.V., et al. Identification of a novel HIV-1 circulating recombinant form CRF157_A6C in Primorsky Territory, Russia. J. Infect. 2024; 88(2): 180–2. https://doi.org/10.1016/j.jinf.2023.11.005
  28. 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
  29. 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
  30. 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(Web Server issue): W193–8. https://doi.org/10.1093/nar/gks414
  31. 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
  32. 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
  33. 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
  34. 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
  35. Lobanov M.Y., Sokolovskiy I.V., Galzitskaya O.V. IsUnstruct: prediction of the residue status to be ordered or disordered in the protein chain by a method based on the Ising model. J. Biomol. Struct. Dyn. 2013; 31(10): 1034–43. https://doi.org/10.1080/07391102.2012.718529
  36. Jumper J., Evans R., Pritzel A., Green T., Figurnov M., Ronneberger O., et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021; 596(7873): 583–9. https://doi.org/10.1038/s41586-021-03819-2
  37. Berezov T.T., Korovkin B.F. Biological Chemistry [Biologicheskaya khimiya]. Moscow: Meditsina; 1998. (in Russian)
  38. 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
  39. Nair M., Gettins L., Fuller M., Kirtley S., Hemelaar J. Global and regional genetic diversity of HIV-1 in 2010-21: systematic review and analysis of prevalence. Lancet Microbe. 2024; 5(11): 100912. https://doi.org/10.1016/S2666-5247(24)00151-4
  40. Bouman J.A., Venner C.M., Walker C., Arts E.J., Regoes R.R. Per-pathogen virulence of HIV-1 subtypes A, C and D. Proc. Biol. Sci. 2023; 290(1998): 20222572. https://doi.org/10.1098/rspb.2022.2572
  41. Sami Saribas A., Cicalese S., Ahooyi T.M., Khalili K., Amini S., Sariyer I.K. HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity. Cell Death Dis. 2017; 8(1): e2542. https://doi.org/10.1038/cddis.2016.467
  42. Cafaro A., Schietroma I., Sernicola L., Belli R., Campagna M., Mancini F., et al. Role of HIV-1 tat protein interactions with host receptors in HIV infection and pathogenesis. Int. J. Mol. Sci. 2024; 25(3): 1704. https://doi.org/10.3390/ijms25031704
  43. Khan N., Geiger J.D. Role of Viral Protein U (VPU) in HIV-1 infection and pathogenesis. Viruses. 2021; 13(8): 1466. https://doi.org/10.3390/v13081466
  44. Ruiz A.P., Ajasin D.O., Ramasamy S., DesMarais V., Eugenin E.A., Prasad V.R. A naturally occurring polymorphism in the HIV-1 tat basic domain inhibits uptake by bystander cells and leads to reduced neuroinflammation. Sci. Rep. 2019; 9(1): 3308. https://doi.org/10.1038/s41598-019-39531-5
  45. 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
  46. Lapavok I.A. Analysis of polymorphism of non-structural regions in the genome of the HIV-1 variant dominant in Russia: Diss. Moscow; 2009. https://elibrary.ru/nkranl (in Russian)
  47. Antonova A.A., Lebedev A.V., Ozhmegova E.N., Shlykova A.V., Lapavok I.A., Kuznetsova A.I. Variability of non-structural proteins of 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)
  48. 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
  49. Shchemelev A.N., Semenov A.V., Ostankova Yu.V., Naidenova E.V., Zueva E.B., Valutite D.E., et al. Genetic diversity of the human immunodeficiency virus (HIV-1) in the Kaliningrad region. Voprosy virusologii. 2022; 67(4): 310–21. https://elibrary.ru/bkswno (in Russian)
  50. Makinson A., Masquelier B., Taieb A., Peytavin G., Waldner-Combernoux A., Collin G., et al. Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA sequences from patients with virological response to HAART. AIDS. 2006; 20(9): 1327–9. https://doi.org/10.1097/01.aids.0000232242.51286.7b
  51. Alidjinou E.K., Deldalle J., Robineau O., Hallaert C., Meybeck A., Huleux T., et al. Routine drug resistance testing in proviral HIV-1 DNA: Prevalence of stop codons and hypermutation, and associated factors. J. Med. Virol. 2019; 91(9): 1684–7. https://doi.org/10.1002/jmv.25474
  52. Bobkova M.R. Defective HIV proviruses: possible involvement in the HIV infection pathogenesis. Voprosy virusologii. 2024; 69(5): 399–414. https://doi.org/10.36233/0507-4088-261 https://elibrary.ru/pselci (in Russia)
  53. Rossenkhan R., Novitsky V., Sebunya T.K., Musonda R., Gashe B.A., Essex M. Viral diversity and diversification of major non-structural genes vif, vpr, vpu, tat exon 1 and rev exon 1 during primary HIV-1 subtype C infection. PLoS One. 2012; 7(5): e35491. https://doi.org/10.1371/journal.pone.0035491
  54. Shen C., Gupta P., Wu H., Chen X., Huang X., Zhou Y., et al. Molecular characterization of the HIV type 1 vpr gene in infected Chinese former blood/plasma donors at different stages of diseases. AIDS Res. Hum. Retroviruses. 2008; 24(4): 661–6. https://doi.org/10.1089/aid.2007.0270

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2. Fig. 1. Schematic representation of Vpr primary structure. M – methionine; E – glutamic acid; D – aspartic acid; T – threonine; L – leucine; A – alanine; V – valine; H – histidine; F – phenylalanine; I – isoleucine; Y – tyrosine; W – tryptophan; R – arginine; S – serine; Vpr T-Helper/CD4+ Epitope region (major) – Vpr region in which predominantly the epitopes have been mapped that are recognized by the immune system for subsequent development of CD4+ T cell response; Vpr CTL/CD8+ Epitope region (major) – Vpr region in which predominantly the epitopes have been mapped that are recognized by the immune system for subsequent development of CD8+ cytotoxic T cell response (https://www.hiv.lanl.gov/content/immunology/maps/ctl/Vpr.html).

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3. Fig. 2. Activities of Vpr protein. RT – reverse transcription; Vpr – Vpr protein; Env – Env protein; PIC – pre-integration complex.

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4. Fig. 3. Genome map with the studied vpr region in samples 1311001072 (а) и 1311001115 (b).

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5. Fig. 4. Phylogenetic analysis of nucleotide sequences of the HIV-1 vpr gene (n = 254, nucleotide substitution model – TIM1 + I + G4). Nucleotide sequences classified as potential unique recombinants are marked with a red asterisk.

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6. Fig. 5. Genome map for the studied vpr region in sample 1311001105. The dotted line indicates the region formed by the HIV-1 fragment of recombinant forms CRF02_AG and CRF63_02A6.

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7. Fig. 6. Consensus sequences of Vpr HIV-1 sub-subtype A6, B and CRF63_02A6 genetic variants aligned with the Vpr_model (sequence of the Vpr protein analyzed in determining the spatial structure [2]). The dots indicate amino acid residues (aa) positions in which the aa in the consensus were the same as in the reference. Non-polar amino acids: G (glycine), A (alanine), V (valine), L (leucine), I (isoleucine), P (proline) – are marked in blue; Polar uncharged amino acids: S (serine), T (threonine), C (cysteine), M (methionine), N (asparagine), Q (glutamine) – green; aromatic amino acids: F (phenylalanine), Tyrosine (Y), W (tryptophan), Histidine (H) – yellow; Polar acidic, negatively charged, amino acids: aspartic acid (D) and glutamic acid (E) – orange; Polar basic, positively charged amino acids: lysine (K), arginine (R) – in red [37, 38].

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8. Fig. 7. The comparison of the tertiary structure of the consensus sequences of sub-subtype A6, subtype B and CRF63_02A6 and Vpr_model, predicted by the IsUnstruct program. a – Vpr_model: unfolded regions from 1 to 15 and from 86 to 96 aa; b – sub-subtype A6 consensus: unfolded regions from 1 to 15 and from 84 to 96 aa; c – subtype B consensus: unfolded regions from 1 to 16 and from 86 to 96 aa; d – CRF63_02A6 consensus: unfolded regions from 1 to 15 and from 86 to 96 aa.

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9. Fig. 8. Monomeric, dimeric and oligomeric forms of Vpr protein in Vpr_model, sub-subtype A6, subtype B and CRF63_02A6 variants predicted by the AlphaFold 2 program. a – monomeric forms of Vpr protein; b – dimeric forms of Vpr protein; c – tetrameric forms of Vpr protein; d – hexameric forms of Vpr protein.

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10. Fig. 9. Alignment of Vpr hexameric structures. Hexamer A6 and Hexamer Vpr_model – hexamer of A6 consensus sequence and hexamer Vpr_model; Hexamer B and Hexamer Vpr_model – hexamer of subtype B consensus sequence and hexamer Vpr_model; Hexamer CRF63_02A6 and Hexamer Vpr_model – hexamer of CRF63_02A6 consensus sequence and hexamer Vpr_model; Hexamer A6 and Hexamer B – hexamer of A6 consensus sequence and hexamer of subtype B consensus sequence; Hexamer A6 and Hexamer CRF63_02A6 – hexamer of A6 consensus sequence and hexamer of CRF63_02A6 consensus sequence; Hexamer B and Hexamer CRF63_02A6 – hexamer of subtype B consensus sequence and hexamer of CRF63_02A6 consensus sequence; The root mean square deviation between Cα atoms for different pairs of hexamers is shown in the figure, which varies from 16.9 Å to 37.8 Å.

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版权所有 © Kuznetsova A.I., Antonova A.A., Makeeva E.A., Kim K.V., Munchak I.M., Mezhenskaya E.N., Orlova-Morozova E.A., Pronin A.Y., Prilipov A.G., Galzitskaya O.V., 2025

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3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».