Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation

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Introduction. The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted.

The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors.

Materials and methods. The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients.

Results and discussion. The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely.

Conclusion. Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

作者简介

A. Kuznetsova

D.I. Ivanovsky Institute of Virology of FSBI “National Reseach 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, Leading Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

I. Munchak

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-4792-8928

Junior Researcher, Laboratory of T-Lymphotropic Viruses, Ivanovsky Institute of Virology

俄罗斯联邦, 123098, Moscow

A. Lebedev

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0001-6787-9345

PhD, Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

A. Tumanov

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-6221-5678

Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

K. Kim

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-4150-2280

Junior Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

A. Antonova

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-9180-9846

Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

E. Ozhmegova

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-3110-0843

Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

A. Pronin

Moscow Regional Center for the Prevention and Control of AIDS and Infectious Diseases

Email: a-myznikova@list.ru
ORCID iD: 0000-0001-6673-1218

PhD, Head Physician

俄罗斯联邦, 129110, Moscow

E. Drobyshevskaya

Moscow Regional Center for the Prevention and Control of AIDS and Infectious Diseases

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-0654-8646

Deputy Head Physician

俄罗斯联邦, 129110, Moscow

E. Kazennova

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0002-7912-4270

Dr Sci, Leading Researcher, Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

M. Bobkova

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

Email: a-myznikova@list.ru
ORCID iD: 0000-0001-5481-8957

Dr Sci, Chief Researcher, Chief of the Laboratory of T-Lymphotropic Viruses

俄罗斯联邦, 123098, Moscow

参考

  1. Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017; 4(8): e349–56. https://doi.org/10.1016/s2352-3018(17)30066-8
  2. Ryom L., Cotter A., De Miguel R., Béguelin C., Podlekareva D., Arribas J.R., et al. 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0. HIV Med. 2020; 21(10): 617–24. https://doi.org/10.1111/hiv.12878
  3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv
  4. Ministry of Health of the Russian Federation. Clinical recommendations. HIV infection in adults; 2020. Available at: https://cr.minzdrav.gov.ru/recomend/79_1 (in Russian)
  5. Cilento M.E., Kirby K.A., Sarafianos S.G. Avoiding drug resistance in HIV reverse transcriptase. Chem. Rev. 2021; 121(6): 3271–96. https://doi.org/10.1021/acs.chemrev.0c00967
  6. Hemelaar J., Elangovan R., Yun J., Dickson-Tetteh L., Fleminger I., Kirtley S., et al. Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis. Lancet Infect. Dis. 2019; 19(2): 143–55. https://doi.org/10.1016/s1473-3099(18)30647-9
  7. 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
  8. Shafer R.W., Rhee S.Y., Pillay D., Miller V., Sandstrom P., Schapiro J.M., et al. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS. 2007; 21(2): 215–23. https://doi.org/10.1097/qad.0b013e328011e691
  9. Wainberg M.A., Brenner B.G. The impact of HIV genetic polymorphisms and subtype differences on the occurrence of resistance to antiretroviral drugs. Mol. Biol. Int. 2012; 2012: 256982. https://doi.org/10.1155/2012/256982
  10. Udeze A.O., Olaleye D.O., Odaibo G.N. Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. PLoS One. 2020; 15(4): e0231031. https://doi.org/10.1371/journal.pone.0231031
  11. Sun Z., Ouyang J., Zhao B., An M., Wang L., Ding H., et al. Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China. BMC Infect. Dis. 2020; 20(1): 178. https://doi.org/10.1186/s12879-020-4808-3
  12. Lapovok I.A., Lopatukhin A.E., Kireev D.E., Kazennova E.V., Lebedev A.V., Bobkova M.R., et al. Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987–2015. Terapevticheskiy arkhiv. 2017; (11): 44–9. https://doi.org/10.17116/terarkh2017891144-49 (in Russian)
  13. Lebedev A., Lebedeva N., Moskaleychik F., Pronin A., Kazennova E., Bobkova M. Human immunodeficiency virus-1 diversity in the Moscow region, Russia: Phylodynamics of the most common subtypes. Front. Microbiol. 2019; 10: 320. https://doi.org/10.3389/fmicb.2019.00320
  14. 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
  15. Bobkov A.F., Kazennova E.V., Selimova L.M., Khanina T.A., Ryabov G.S., Bobkova M.R., et al. Temporal trends in the HIV-1 epidemic in Russia: predominance of subtype A. J. Med. Virol. 2004; 74(2): 191–6. https://doi.org/10.1002/jmv.20177
  16. Ozhmegova E.N., Antonova A.A., Lebedev A.V., Mel’nikova T.N., Krylova T.V., Kazachek A.V., et al. Genetic profile of HIV-1 in the Vologda region: domination of CRF03_AB and rapid distribution of URFS. VICh-infektsiya i immunosupressii. 2020; 12(2): 79–88. https://doi.org/10.22328/2077-9828-2020-12-2-79-88 (in Russian)
  17. Kazennova E., Laga V., Lapovok I., Glushchenko N., Neshumaev D., Vasilyev A., et al. HIV-1 genetic variants in the Russian Far East. AIDS Res. Hum. Retroviruses. 2014; 30(8): 742–52. https://doi.org/10.1089/aid.2013.0194
  18. Maksimenko L.V., Totmenin A.V., Gashnikova M.P., Astakhova E.M., Skudarnov S.E., Ostapova T.S., et al. Genetic diversity of HIV-1 in Krasnoyarsk Krai: Area with high levels of HIV-1 recombination in Russia. Biomed. Res. Int. 2020; 2020: 9057541. https://doi.org/10.1155/2020/9057541
  19. Tumanov A.S., Kazennova E.V., Gromov K.B., Lomakina E.A., Zozulya E.Yu., Bersenev P.G., et al. The molecular epidemiological analysis of HIV infection in Sakhalin region, Russia. VICh-infektsiya i immunosupressii. 2017; 9(3): 113–20. https://doi.org/10.22328/2077-9828-2017-9-3-113-120 (in Russian)
  20. Gashnikova N.M., Bogachev V.V., Baryshev P.B., Totmenin A.V., Gashnikova M.P., Kazachinskaya A.G., et al. A rapid expansion of HIV-1 CRF63_02A1 among newly diagnosed HIV-infected individuals in the Tomsk Region, Russia. AIDS Res. Hum. Retroviruses. 2015; 31(4): 456–60. https://doi.org/10.1089/aid.2014.0375
  21. Shcherbakova N.S., Shalamova L.A., Delgado E., Fernández-García A., Vega Y., Karpenko L.I., et al. Short communication: Molecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia. AIDS Res. Hum. Retroviruses. 2014; 30(9): 912–9. https://doi.org/10.1089/aid.2014.0075
  22. Baryshev P.B., Bogachev V.V., Gashnikova N.M. HIV-1 genetic diversity in Russia: CRF63_02A1, a new HIV type 1 genetic variant spreading in Siberia. AIDS Res. Hum. Retroviruses. 2014; 30(6): 592–7. https://doi.org/10.1089/aid.2013.0196
  23. Kazennova E.V., Lapovok I.A., Laga V.Yu., Vasil’ev A.V., Bobkova M.R. Natural polymorphisms of HIV-1 IDU-A variant pol gene. VICh-infektsiya i immunosupressii. 2012; 4(4): 44–51. (in Russian)
  24. Kirichenko A., Lapovok I., Baryshev P., van de Vijver D.A.M.C., van Kampen J.J.A., Boucher C.A.B., et al. Genetic features of HIV-1 integrase sub-subtype A6 predominant in Russia and predicted susceptibility to INSTIs. Viruses. 2020; 12(8): 838. https://doi.org/10.3390/v12080838
  25. Kazennova E.V., Vasil’ev A.V., Bobkova M.R. The forecast of the effectiveness of the drug Bevirimat in Russia. Voprosy virusologii. 2010; 55(3): 37–41. (in Russian)
  26. Vasil’ev A.V., Akhmerov K.R., Salamov G.G., Kazennova E.V., Bobkova M.R. Analysis of the polymorphism of the genome region of HIV-1 encoding the fusion protein. Voprosy virusologii. 2012; 57(4): 9–13. (in Russian)
  27. Vasil’ev A.V, Kazennova E.V., Bobkova M.R. Analysis of the prevalence of drug resistance mutations to drugs belonging to the class of CCR5 co-receptor antagonists among HIV-1 variants in Russia. Voprosy virusologii. 2011; (3): 32–7. (in Russian)
  28. Gromov K.B., Kireev D.E., Murzakova A.V., Lopatukhin A.E., Kazennova E.V., Bobkova M.R. Analysis of HIV-1 (human immunodeficiency VIRUS-1, lentivirus, orthoretrovirinae, retroviridae) NEF protein polymorphism of variants circulating in the former USSR countries. Voprosy virusologii. 2019; 64(6): 281–90. https://doi.org/10.36233/0507-4088-2019-64-6-281-290 (in Russian)
  29. 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): 452–64. https://doi.org/10.36233/0507-4088-83 (in Russian)
  30. Xu H.T., Colby-Germinario S.P., Asahchop E.L., Oliveira M., McCallum M., Schader S.M., et al. Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine. Antimicrob. Agents Chemother. 2013; 57(7): 3100–9. https://doi.org/10.1128/aac.00348-13
  31. Maldonado J.O., Mansky L.M. The HIV-1 Reverse transcriptase A62V mutation influences replication fidelity and viral fitness in the context of multi-drug-resistant mutations. Viruses. 2018; 10(7): 376. https://doi.org/10.3390/v10070376
  32. Garrido C., Villacian J., Zahonero N., Pattery T., Garcia F., Gutierrez F., et al. Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens. Antimicrob. Agents Chemother. 2012; 56(6): 2873–8. https://doi.org/10.1128/aac.06170-11
  33. McFadden W.M., Snyder A.A., Kirby K.A., Tedbury P.R., Raj M., Wang Z., et al. Rotten to the core: antivirals targeting the HIV-1 capsid core. Retrovirology. 2021; 18(1): 41. https://doi.org/10.1186/s12977-021-00583-z
  34. Troyano-Hernáez P., Reinosa R., Holguín Á. HIV capsid protein genetic diversity across HIV-1 variants and impact on new capsid-inhibitor lenacapavir. Front. Microbiol. 2022; 13: 854974. https://doi.org/10.3389/fmicb.2022.854974
  35. Gray E.R., Bain R., Varsaneux O., Peeling R.W., Stevens M.M., McKendry R.A. p24 revisited: a landscape review of antigen detection for early HIV diagnosis. AIDS. 2018; 32(15): 2089–102. https://doi.org/10.1097/qad.0000000000001982
  36. Larijani M.S., Sadat S.M., Bolhassani A., Khodaie A., Pouriayevali M.H., Ramezani A. HIV-1 p24-nef DNA vaccine plus protein boost expands T-Cell responses in BALB/c. Curr. Drug Deliv. 2021; 18(7): 1014–21. https://doi.org/10.2174/1567201818666210101113601
  37. Sadat Larijani M., Ramezani A., Mashhadi Abolghasem Shirazi M., Bolhassani A., Pouriayevali M.H., Shahbazi S., et al. Evaluation of transduced dendritic cells expressing HIV-1 p24-Nef antigens in HIV-specific cytotoxic T cells induction as a therapeutic candidate vaccine. Virus Res. 2021; 298: 198403. https://doi.org/10.1016/j.virusres.2021.198403
  38. Novikova M., Zhang Y., Freed E.O., Peng K. Multiple roles of HIV-1 capsid during the virus replication cycle. Virol. Sin. 2019; 34(2): 119–34. https://doi.org/10.1007/s12250-019-00095-3
  39. Rihn S.J., Wilson S.J., Loman N.J., Alim M., Bakker S.E., Bhella D., et al. Extreme genetic fragility of the HIV-1 capsid. PLoS Pathog. 2013; 9(6): e1003461. https://doi.org/10.1371/journal.ppat.1003461
  40. Braaten D., Luban J. Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells. EMBO J. 2001; 20(6): 1300–9. https://doi.org/10.1093/emboj/20.6.1300
  41. Saito A., Yamashita M. HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules. Retrovirology. 2021; 18(1): 32. https://doi.org/10.1186/s12977-021-00577-x
  42. Dvory-Sobol H., Shaik N., Callebaut C., Rhee M.S. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. Curr. Opin. HIV AIDS. 2022; 17(1): 15–21. https://doi.org/10.1097/coh.0000000000000713
  43. Gilead. Pipeline Gilead – 2022. Available at: https://www.gilead.com/science-and-medicine/pipeline
  44. Link J.O., Rhee M.S., Tse W.C., Zheng J., Somoza J.R., Rowe W., et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020; 584(7822): 614–8. https://doi.org/10.1038/s41586-020-2443-1
  45. Yant S.R., Mulato A., Hansen D., Thielen A., Schroeder S.D. In vitro resistance profile of GS-6207, a first-in-class picomolar HIV capsid inhibitor in clinical development as a novel long-acting antiretroviral agent. In: Tenth IAS Conference on HIV Science. Mexico City; 2019.
  46. Marcelin A.G., Charpentier C., Jary A., Perrier M., Margot N., Callebaut C., et al. Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients. J. Antimicrob. Chemother. 2020; 75(6): 1588–90. https://doi.org/10.1093/jac/dkaa060
  47. 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
  48. 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/16.3.1215
  49. 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
  50. Jin H., Sun Y., Li D., Lin M.H., Lor M., Rustanti L., et al. Strong in vivo inhibition of HIV-1 replication by nullbasic, a Tat mutant. mBio. 2019; 10(4): e01769–19. https://doi.org/10.1128/mbio.01769-19
  51. Leoz M., Kukanja P., Luo Z., Huang F., Cary D.C., Peterlin B.M., et al. HEXIM1-Tat chimera inhibits HIV-1 replication. PLoS Pathog. 2018; 14(11): e1007402. https://doi.org/10.1371/journal.ppat.1007402
  52. Sgadari C., Monini P., Tripiciano A., Picconi O., Casabianca A., Orlandi C., et al. Continued decay of HIV proviral DNA upon vaccination with HIV-1 Tat of subjects on long-term ART: An 8-Year follow-up study. Front. Immunol. 2019; 10: 233. https://doi.org/10.3389/fimmu.2019.00233
  53. Loret E.P., Darque A., Jouve E., Loret E.A., Nicolino-Brunet C., Morange S., et al. Intradermal injection of a Tat Oyi-based therapeutic HIV vaccine reduces of 1.5 log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART interruption in a phase I/II randomized controlled clinical trial. Retrovirology. 2016; 13: 21. https://doi.org/10.1186/s12977-016-0251-3
  54. Liitsola K., Holm K., Bobkov A., Pokrovsky V., Smolskaya T., Leinikki P., et al. An AB recombinant and its parental HIV type 1 strains in the area of the former Soviet Union: low requirements for sequence identity in recombination. UNAIDS Virus Isolation Network. AIDS Res. Hum. Retroviruses. 2000; 16(11): 1047–53. https://doi.org/10.1089/08892220050075309
  55. Baryshev P.B., Bogachev V.V., Gashnikova N.M. HIV-1 genetic diversity in Russia: CRF63_02A1, a new HIV type 1 genetic variant spreading in Siberia. AIDS Res. Hum. Retroviruses. 2014; 30(6): 592–7. https://doi.org/10.1089/aid.2013.0196
  56. Knops E., Däumer M., Awerkiew S., Kartashev V., Schülter E., Kutsev S., et al. Evolution of protease inhibitor resistance in the gag and pol genes of HIV subtype G isolates. J. Antimicrob. Chemother. 2010; 65(7): 1472–6. https://doi.org/10.1093/jac/dkq129
  57. Selyutina A., Persaud M., Simons L.M., Bulnes-Ramos A., Buffone C., Martinez-Lopez A., et al. Cyclophilin A prevents HIV-1 restriction in lymphocytes by blocking human TRIM5α binding to the viral core. Cell Rep. 2020; 30(11): 3766–77.e6. https://doi.org/10.1016/j.celrep.2020.02.100

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