aidsВИЧ-инфекция и иммуносупрессииHIV Infection and Immunosuppressive Disorders2077-9828Baltic Medical Education Center10.22328/2077-9828-2023-15-3-26-37aids-823Research ArticleАНАЛИТИЧЕСКИЕ ОБЗОРЫANALYTICAL REVIEWSРоль полиморфизма ВИЧ-1 в патогенезе заболеванияThe role of HIV-1 polymorphism in the pathogenesis of the diseasehttps://orcid.org/0000-0001-5299-3081КузнецоваА. И.KuznetsovaA. I.

Кузнецова Анна Игоревна — кандидат биологических наук, ведущий научный сотрудник, заведующая лабораторией вирусов лейкозов 

123098, Москва, ул. Гамалеи, д. 18

Moscow

a-myznikova@list.ruНациональный исследовательский центр эпидемиологии и микробиологии имени почетного академика Н. Ф. ГамалеиРоссияN. F. Gamaleya National Research Center for Epidemiology and MicrobiologyRussian Federation2023211020231532637Copyright © Кузнецова А.И., 20232023Кузнецова А.И.Kuznetsova A.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://hiv.bmoc-spb.ru/jour/article/view/823

Одним из определяющих свойств ВИЧ-1 является высокая генетическая изменчивость, способствующая возникновению лекарственной устойчивости и разнообразных форм вируса. В мире различные варианты ВИЧ-1 распределяются неравномерно. В России циркулируют характерные для нашей страны и некоторых стран бывшего СССР варианты вируса, которые отличаются от вариантов ВИЧ-1, циркулирующих в других странах мира. На протяжении многих лет проводятся исследования особенностей влияния различных вариантов ВИЧ-1 на патогенез, в рамках которых выявляют и изучают мутации полиморфизма у  различных субтипов и  рекомбинантных форм. Основными объектами антиретровирусной терапии в настоящее время являются структурные белки ВИЧ-1, преимущественно белки-ферменты, полиморфные мутации в которых могут оказывать влияние на степень чувствительности вируса к антиретровирусной терапии. Неструктурные белки ВИЧ-1 участвуют в репликации вируса и его защите от иммунной системы хозяина, поступают в кровоток и ткани, вызывая развитие воспаления. Полиморфные мутации в неструктурных белках могут влиять на степень прогрессирования ВИЧинфекции и на степень развития сопутствующих соматических заболеваний. В настоящее время неструктурные белки рассматриваются как объекты для создания терапевтических средств, а выявление полиморфных мутаций в неструктурных белках у различных вариантов ВИЧ-1 представляет основу для такого рода разработок. Таким образом, изучение полиморфизма как структурных, так и неструктурных белков ВИЧ-1 является перспективным направлением исследований в будущем.

High genetic variability is one of the defining HIV-1 properties. It contributes to the appearance of drug resistance and to the formation of various HIV variants. In the world, the different variants of HIV-1 are distributed unevenly. In Russia there are circulating unique virus variants which are characteristic for our country and some countries of the former USSR and which are difference from HIV-1 variants circulating in other countries of the world. For many years, the studies aimed on the analysis of the influence of various HIV-1 variants on pathogenesis have been conducted. Within the framework of these studies, the polymorphism mutations in different subtypes and recombinant forms have been detected. Currently the main objects of antiretroviral therapy are HIV-1 structural proteins, mainly enzyme proteins, thus polymorphic mutations in which could affect the degree of virus sensitivity to antiretroviral therapy. Non-structural HIV-1 proteins are involved in virus replication and virus protection from the host immune system, enter the bloodstream and tissues, causing the development of inflammation. The polymorphic mutations in non-structural proteins could affect the degree of HIV infection progression and the development of concomitant somatic diseases. Today, nonstructural proteins are considered as objects for the creation of therapeutic agents, thus the identification of polymorphic mutations in nonstructural proteins in different HIV-1 variants is a basis for such developments. Thus, the study of polymorphism of both structural and non-structural HIV-1 proteins is a promising area of research in the future.

ВИЧ-1полиморфизмпатогенезHIV-1polymorphismpathogenesisИсследование выполнено за счет средств гранта Российского научного фонда № 23–15–00027, https://rscf.ru/project/23–15–00027/.ReferencesMcLaren P.J., Fellay J. HIV-1 and human genetic variation // Nat. Rev. Genet. 2021. Vol. 22. Р. 645–657. https://doi.org/10.1038/s41576-021-00378-0.McLaren P.J., Fellay J. HIV-1 and human genetic variation // Nat. Rev. Genet. 2021. Vol. 22. Р. 645–657. https://doi.org/10.1038/s41576- 021-00378-0.Agosto L.M., Henderson A.J. CD4+ T Cell Subsets and Pathways to HIV Latency // AIDS Res. Hum. Retroviruses. 2018. Vol. 34, No. 9. Р. 780–789. doi: 10.1089/AID.2018.0105.Agosto L.M., Henderson A.J. CD4+ T Cell Subsets and Pathways to HIV Latency // AIDS Res. Hum. Retroviruses. 2018. Vol. 34, No. 9. Р. 780–789. doi: 10.1089/AID.2018.0105.Cilento M.E., Kirby K.A., Sarafianos S.G. Avoiding drug resistance in HIV reverse transcriptase // Chem. Rev. 2021. Vol. 121, No. 6. Р. 3271– 3296. https://doi.org/10.1021/acs.chemrev.0c00967.Cilento M.E., Kirby K.A., Sarafianos S.G. Avoiding drug resistance in HIV reverse transcriptase // Chem. Rev. 2021. Vol. 121, No. 6. Р. 3271– 3296. https://doi.org/10.1021/acs.chemrev.0c00967.Бобкова М.Р. Генетическое разнообразие вирусов иммунодефицита человека и антиретровирусная терапия // Терапевтический архив. 2016. Т. 88, № 11. Р. 103–111. https://doi.org/10.17116/terarkh20168811103-111.Бобкова М.Р. Генетическое разнообразие вирусов иммунодефицита человека и антиретровирусная терапия // Терапевтический архив. 2016. Т. 88, № 11. Р. 103–111. https://doi.org/10.17116/terarkh20168811103-111.Désiré N., Cerutti L., Le Hingrat Q., Perrier M., Emler S., Calvez V., Descamps D., Marcelin A-G., Hué S., Visseaux B. Characterization update of HIV-1 M subtypes diversity and proposal for subtypes A and D sub-subtypes reclassification // Retrovirology. 2018. Vol. 15. Р. 80. https://doi.org/10.1186/s12977-018-0461-y.Désiré N., Cerutti L., Le Hingrat Q., Perrier M., Emler S., Calvez V., Descamps D., Marcelin A-G., Hué S., Visseaux B. Characterization update of HIV-1 M subtypes diversity and proposal for subtypes A and D sub-subtypes reclassification // Retrovirology. 2018. Vol. 15. Р. 80. https://doi.org/10.1186/s12977-018-0461-y.Mendes Da Silva R.K., Monteiro de Pina Araujo I.I., Venegas Maciera K., Gonçalves Morgado M., Lindenmeyer Guimarães M. Genetic Characterization of a New HIV-1 Sub-Subtype A in Cabo Verde, Denominated A8 // Viruses. 2021. Vol. 13. Р. 1093. https://doi.org/10.3390/v13061093.Mendes Da Silva R.K., Monteiro de Pina Araujo I.I., Venegas Maciera K., Gonçalves Morgado M., Lindenmeyer Guimarães M. Genetic Characterization of a New HIV-1 Sub-Subtype A in Cabo Verde, Denominated A8 // Viruses. 2021. Vol. 13. Р. 1093. https://doi.org/10.3390/ v13061093.Yamaguchi J., Vallari A., McArthur C., Sthreshley L., Cloherty G.A., Berg M.G., Rodgers M.A. Brief Report: Complete Genome Sequence of CG0018a-01 Establishes HIV-1 Subtype L // J. Acquir. Immune Defic. Syndr. 2020. Vol. 83, No. 3. Р. 319–322. doi: 10.1097/QAI.0000000000002246.Yamaguchi J., Vallari A., McArthur C., Sthreshley L., Cloherty G.A., Berg M.G., Rodgers M.A. Brief Report: Complete Genome Sequence of CG0018a-01 Establishes HIV-1 Subtype L // J. Acquir. Immune Defic. Syndr. 2020. Vol. 83, No. 3. Р. 319–322. doi: 10.1097/QAI.0000000000002246.Hemelaar J., Elangovan R., Yun J., Dickson-Tetteh L., Fleminger I., Kirtley S., Williams B., Gouws-Williams E., Ghys P.D. WHO-UNAIDS Network for HIV Isolation Characterisation. Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis // Lancet Infect. Dis. 2019. Vol. 19, No. 2. Р. 143–155. doi: 10.1016/S1473-3099(18)30647-9.Hemelaar J., Elangovan R., Yun J., Dickson-Tetteh L., Fleminger I., Kirtley S., Williams B., Gouws-Williams E., Ghys P.D. WHO-UNAIDS Network for HIV Isolation Characterisation. Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis // Lancet Infect. Dis. 2019. Vol. 19, No. 2. Р. 143–155. doi: 10.1016/S1473-3099(18)30647-9.Shafer R.W., Rhee S.Y., Pillay D., Miller V., Sandstrom P., Schapiro J.M., Kuritzkes D.R., Bennett D. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance // AIDS. 2007. Vol. 21, No. 2. Р. 215–223. doi: 10.1097/QAD.0b013e328011e691.Shafer R.W., Rhee S.Y., Pillay D., Miller V., Sandstrom P., Schapiro J.M., Kuritzkes D.R., Bennett D. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance // AIDS. 2007. Vol. 21, No. 2. Р. 215–223. doi: 10.1097/QAD.0b013e328011e691.Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide // Curr. Opin. HIV AIDS. 2019. Vol. 14, No. 3. Р. 153–160. doi: 10.1097/COH.0000000000000534.Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide // Curr. Opin. HIV AIDS. 2019. Vol. 14, No. 3. Р. 153–160. doi: 10.1097/COH.0000000000000534.Salvaña E.M.T., Dungca N.T., Arevalo G., Li K., Francisco C., Penalosa C., Dela Tonga A., Leyritana K., Solante R., Tactacan-Abrenica R.J., Lim J., Alejandria M., Palaypayon N., Schwem B. HIV-1 Subtype Shift in the Philippines is Associated With High Transmitted Drug Resistance, High Viral Loads, and Fast Immunologic Decline // Int. J. Infect. Dis. 2022. Vol. 122. Р. 936–943. doi: 10.1016/j.ijid.2022.06.048.Salvaña E.M.T., Dungca N.T., Arevalo G., Li K., Francisco C., Penalosa C., Dela Tonga A., Leyritana K., Solante R., Tactacan-Abrenica R.J., Lim J., Alejandria M., Palaypayon N., Schwem B. HIV-1 Subtype Shift in the Philippines is Associated With High Transmitted Drug Resistance, High Viral Loads, and Fast Immunologic Decline // Int. J. Infect. Dis. 2022. Vol. 122. Р. 936–943. doi: 10.1016/j.ijid.2022.06.048.Bobkov A., Kazennova E., Selimova L., Bobkova M., Khanina T., Ladnaya N., Kravchenko A., Pokrovsky V., Cheingsong-Popov R., Weber J. A sudden epidemic of HIV type 1 among injecting drug users in the former Soviet Union: identification of subtype A, subtype B, and novel gagA/envB recombinants // AIDS Res. Hum. Retroviruses. 1998. Vol. 14. Р. 669–676. doi: 10.1089/aid.1998.14.669.Bobkov A., Kazennova E., Selimova L., Bobkova M., Khanina T., Ladnaya N., Kravchenko A., Pokrovsky V., Cheingsong-Popov R., Weber J. A sudden epidemic of HIV type 1 among injecting drug users in the former Soviet Union: identification of subtype A, subtype B, and novel gagA/envB recombinants // AIDS Res. Hum. Retroviruses. 1998. Vol. 14. Р. 669–676. doi: 10.1089/aid.1998.14.669.Foley B.T., Leitner T., Paraskevis D. and Peeters M. Primate immunodeficiency virus classification and nomenclature: review // Infect. Genet. Evol. 2016. Vol. 46. Р. 150–158. doi: 10.1016/j.meegid.2016.10.018.Foley B.T., Leitner T., Paraskevis D. and Peeters M. Primate immunodeficiency virus classification and nomenclature: review // Infect. Genet. Evol. 2016. Vol. 46. Р. 150–158. doi: 10.1016/j.meegid.2016.10.018.Лаповок И.А., Лопатухин А.Э., Киреев Д.Е., Казеннова Е.В., Лебедев А.В., Бобкова М.Р., Коломеец А.Н., Турбина Г.И., Шипулин Г.А., Ладная Н.Н., Покровский В.В. Молекулярно-эпидемиологический анализ вариантов ВИЧ-1, циркулировавших в России в 1987–2015 гг. // Терапевтический архив. 2017. Т. 89, № 11. Р. 44–49. doi: 10.17116/terarkh2017891144-49 doi: 10.17116/terarkh2017891144-49.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. Therapeutic archive, 2017, Vol. 89, No. 11, рр. 44–49 (In Russ.) doi: 10.17116/terarkh2017891144-49 doi: 10.17116/terarkh2017891144-49.Bobkov A.F., Kazennova E.V., Selimova L.M., Khanina T.A., Ryabov G.S., Bobkova M.R., Sukhanova A.L, Kravchenko A.V., Ladnaya N.N., Weber J.N., Pokrovsky V.V. Temporal trends in the HIV-1 epidemic in Russia: predominance of subtype A // J. Med. Virol. 2004. Vol. 74, No. 2. Р. 191–6. https://doi.org/10.1002/jmv.20177.Bobkov A.F., Kazennova E.V., Selimova L.M., Khanina T.A., Ryabov G.S., Bobkova M.R., Sukhanova A.L, Kravchenko A.V., Ladnaya N.N., Weber J.N., Pokrovsky V.V. Temporal trends in the HIV-1 epidemic in Russia: predominance of subtype A // J. Med. Virol. 2004. Vol. 74, No. 2. Р. 191–6. https://doi.org/10.1002/jmv.20177.Ожмегова Е.Н., Антонова А.А., Лебедев А.В., Мельникова Т.Н., Крылова Т.В., Казачек А.В., Ширяева Н. А., Кириллова И. Л., Казеннова Е.В., Бобкова М.Р. Генетический профиль ВИЧ-1 в Вологодской области: доминирование CRF03_AB и быстрое распространение URFs // ВИЧ-инфекция и иммуносупрессии. 2020. Т.12, № 2. С. 79–88. https://doi.org/10.22328/2077-9828-2020-12-2-79-88.Ozhmegova E.N., Antonova A.A., Lebedev A.V., Melnikova T.N., Krylova T.V., Kazachek A.V., Shiryaeva N.A., Kirillova I.L., Kazennova E.V., Bobkova M.R. Genetic Profile of HIV-1 in the Vologda Region: Domination of CRF03_AB and Rapid Distribution of URFs.HIV Infection and Immunosuppressive Disorders, 2020, Vol.12, No. 2, рр. 79–88 (In Russ.) https://doi.org/10.22328/2077-9828-2020-12-2-79-88.Щемелев А.Н., Семенов А.В., Останкова Ю.В., Найденова Е.В., Зуева Е.Б., Валутите Д.Э., Чурина М.А., Виролайнен П.А., Тотолян А.А. Генетическое разнообразие вируса иммунодефицита человека (ВИЧ-1) в Калининградской области // Вопросы вирусологии. 2022. Т. 67, № 4. С. 310–321. doi: https://doi.org/10.36233/0507-4088-119.Shchemelev A.N., Semenov A.V., Ostankova Yu.V., Naidenova E.V., Zueva E.B., Valutite D.E., Churina M.A., Virolainen P.A., Totolian A.A. Genetic diversity of the human immunodeficiency virus (HIV-1) in the Kaliningrad region. Problems of Virology (Voprosy Virusologii), 2022, Vol. 67, No. 4, рр. 310–321. doi: https://doi. org/10.36233/0507-4088-119.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. Vol. 30, No. 6. Р. 592–597. doi: 10.1089/aid.2013.0196.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. Vol. 30, No. 6. Р. 592–597. doi: 10.1089/aid.2013.0196.Gashnikova N.M., Bogachev V.V., Baryshev P.B., Totmenin A.V., Gashnikova M.P., Kazachinskaya A.G., Ismailova T.N., Stepanova S.A., Chernov A.S., Mikheev V.N. A rapid expansion of HIV-1 CRF63_02A1 among newly diagnosed HIV-infected individuals in the Tomsk Region, Russia // AIDS Res Hum Retroviruses. 2015. Vol. 31, No. 4. Р. 456–460. doi: 10.1089/AID.2014.0375.Gashnikova N.M., Bogachev V.V., Baryshev P.B., Totmenin A.V., Gashnikova M.P., Kazachinskaya A.G., Ismailova T.N., Stepanova S.A., Chernov A.S., Mikheev V.N. A rapid expansion of HIV-1 CRF63_02A1 among newly diagnosed HIV-infected individuals in the Tomsk Region, Russia // AIDS Res Hum Retroviruses. 2015. Vol. 31, No. 4. Р. 456–460. doi: 10.1089/AID.2014.0375.Gashnikova N.M., Zyryanova D.P., Astakhova E.M., Ivlev V.V., Gashnikova M.P., Moskaleva N.V., Aikin S.S., Bulatova T.N., Pustylnikov S.V., Bocharov E.F., Totmenin A.V. Predominance of CRF63_02A1 and multiple patterns of unique recombinant forms of CRF63_A1 among individuals with newly diagnosed HIV-1 infection in Kemerovo Oblast, Russia // Arch. Virol. 2017. Vol. 162, No. 2. Р. 379–390. doi: 10.1007/s00705-016-3120-4.Gashnikova N.M., Zyryanova D.P., Astakhova E.M., Ivlev V.V., Gashnikova M.P., Moskaleva N.V., Aikin S.S., Bulatova T.N., Pustylnikov S.V., Bocharov E.F., Totmenin A.V. Predominance of CRF63_02A1 and multiple patterns of unique recombinant forms of CRF63_A1 among individuals with newly diagnosed HIV-1 infection in Kemerovo Oblast, Russia // Arch. Virol. 2017. Vol. 162, No. 2. Р. 379–390. doi: 10.1007/s00705-016-3120-4.Maksimenko L.V., Sivay M.V., Totmenin A.V., Shvalov A.N., Skudarnov S.E., Ostapova T.S., Yaschenko S.V., Maksutov R.A., Gashnikova N.M. Novel HIV-1 A6/B recombinant forms (CRF133_A6B and URF_A6/B) circulating in Krasnoyarsk region, Russia // J. Infect. 2022. Vol. 85, No. 6. Р. 702–769. doi: 10.1016/j.jinf.2022.10.001.Maksimenko L.V., Sivay M.V., Totmenin A.V., Shvalov A.N., Skudarnov S.E., Ostapova T.S., Yaschenko S.V., Maksutov R.A., Gashnikova N.M. Novel HIV-1 A6/B recombinant forms (CRF133_A6B and URF_A6/B) circulating in Krasnoyarsk region, Russia // J. Infect. 2022. Vol. 85, No. 6. Р. 702–769. doi: 10.1016/j.jinf.2022.10.001.German Advisory Committee Blood (Arbeitskreis Blut), Subgroup ‘Assessment of Pathogens Transmissible by Blood’. Human Immunodeficiency Virus (HIV) // Transfus. Med. Hemother. 2016. Vol. 43. Р. 203–222. doi: 10.1159/000445852.German Advisory Committee Blood (Arbeitskreis Blut), Subgroup ‘Assessment of Pathogens Transmissible by Blood’. Human Immunodeficiency Virus (HIV) // Transfus. Med. Hemother. 2016. Vol. 43. Р. 203–222. doi: 10.1159/000445852.Faust T.B., Binning J.M., Gross J.D., Frankel A.D. Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription // Annu Rev Virol. 2017. Vol. 4, No. 1. Р. 241–260. doi: 10.1146/annurev-virology101416-041654.Faust T.B., Binning J.M., Gross J.D., Frankel A.D. Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription // Annu Rev Virol. 2017. Vol. 4, No. 1. Р. 241–260. doi: 10.1146/annurev-virology101416-041654.Maeda K., Das D., Kobayakawa T., Tamamura H., Takeuchi H. Discovery and Development of Anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication // Curr. Top. Med. Chem. 2019. Vol. 19, No. 18. Р. 1621–1649. doi: 10.2174/1568026619666190712204603.Maeda K., Das D., Kobayakawa T., Tamamura H., Takeuchi H. Discovery and Development of Anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication // Curr. Top. Med. Chem. 2019. Vol. 19, No. 18. Р. 1621–1649. doi: 10.2174/1568026619666190712204603.Казеннова Е.В., Лаповок И.А., Лага В.Ю., Васильев А.В., Бобкова М.Р. Естественные полиморфизмы гена pol варианта ВИЧ 1 IDU A // ВИЧ-инфекция и иммуносупрессии. 2012. Т. 4, № 4. С. 44–51.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. HIV Infection and Immunosuppressive Disorders, 2012. Vol. 44. Р. 44–51. (In Russ.)Васильев А.В., Ахмеров К.Р., Саламов Г.Г., Казеннова Е.В., Бобкова М.Р. Анализ полиморфизма области генома ВИЧ-1, кодирующей белок слияния // Вопросы вирусологии. 2012. Т. 57, № 4. Р. 9–13.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, Vol. 57, No. 4, рр. 9–13 (In Russ.)Казеннова Е. В., Васильев А.В., Бобкова М.Р. Прогноз эффективности применения препарата Бевиримат для лечения ВИЧ-инфекции в России // Вопросы вирусологии. 2010. Т. 55, № 3. С. 37–41.Kazennova E.V., Vasil’ev A.V., Bobkova M.R. The prognosis of the effectiveness of Bevirimat for the treatment of HIV infection in Russia. Voprosy virusologii, 2010, Vol. 55, No. 3, рр. 37–41 (In Russ.)Lapovok I., Laga V., Kazennova.E and Bobkova M. HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries // Current HIV Research. 2017. Vol. 15. Р. 1–9. doi: 10.2174/1570162X15666170815162052.Lapovok I., Laga V., Kazennova.E and Bobkova M. HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries // Current HIV Research. 2017. Vol. 15. Р. 1–9. doi: 10.2174/1570162X15666170815162052.Kolomeets A.N., Vargheseb V., Lemeyc P., Bobkova M.R. and Shafer R.W. A uniquely prevalent non-nucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses // AIDS. 2014. Vol. 28, No. 17. Р. F1-F8. doi: 10.1097/QAD.0000000000000485.Kolomeets A.N., Vargheseb V., Lemeyc P., Bobkova M.R. and Shafer R.W. A uniquely prevalent non-nucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses // AIDS. 2014. Vol. 28, No. 17. Р. F1-F8. doi: 10.1097/QAD.0000000000000485.Kirichenko A., Lapovok I., Baryshev P., van de Vijver D A. M. C., van Kampen J. J. A., Boucher C. A. B., Paraskevis D. and Kireev D. Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs // Viruses. 2020. Vol. 12. Р. 838. doi: 10.3390/v12080838.Kirichenko A., Lapovok I., Baryshev P., van de Vijver D A. M. C., van Kampen J. J. A., Boucher C. A. B., Paraskevis D. and Kireev D. Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs // Viruses. 2020. Vol. 12. Р. 838. doi: 10.3390/v12080838.Kirichenko A., Kireev D., Lapovok I., Shlykova A., Lopatukhin A., Pokrovskaya A., Bobkova M., Antonova A., Kuznetsova A., Ozhmegova E., Shtrek S., Sannikov A., Zaytseva N., Peksheva O., Piterskiy M., Semenov A., Turbina G., Filoniuk N., Shemshura A., Kulagin V., Kolpakov D., Suladze A., Kotova V., Balakhontseva L., Pokrovsky V. and Akimkin V. HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006–2022 // Viruses. 2023. Vol. 15, No. 991. https://doi.org/10.3390/v15040991.Kirichenko A., Kireev D., Lapovok I., Shlykova A., Lopatukhin A., Pokrovskaya A., Bobkova M., Antonova A., Kuznetsova A., Ozhmegova E., Shtrek S., Sannikov A., Zaytseva N., Peksheva O., Piterskiy M., Semenov A., Turbina G., Filoniuk N., Shemshura A., Kulagin V., Kolpakov D., Suladze A., Kotova V., Balakhontseva L., Pokrovsky V. and Akimkin V. HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006–2022 // Viruses. 2023. Vol. 15, No. 991. https://doi.org/10.3390/v15040991.Schlösser M., Kartashev V.V., Mikkola V.H., Shemshura A., Saukhat S., Kolpakov D., Suladze A., Tverdokhlebova T., Hutt K., Heger E., Knops E., Böhm M., Di Cristanziano V., Kaiser R., Sönnerborg A., Zazzi M., Bobkova M., Sierra S. HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia // Viruses. 2020. Vol. 12, No. 4. Р. 475. doi: 10.3390/v12040475.Schlösser M., Kartashev V.V., Mikkola V.H., Shemshura A., Saukhat S., Kolpakov D., Suladze A., Tverdokhlebova T., Hutt K., Heger E., Knops E., Böhm M., Di Cristanziano V., Kaiser R., Sönnerborg A., Zazzi M., Bobkova M., Sierra S. HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia // Viruses. 2020. Vol. 12, No. 4. Р. 475. doi: 10.3390/v12040475.Xu H.T., Colby-Germinario S.P., Asahchop E.L., Oliveira M., McCallum M., Schader S.M., Han Y., Quan Y., Sarafianos S.G., Wainberg M.A. 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. Vol. 57, No. 7. Р. 3100–3109. doi: 10.1128/AAC.00348-13.Xu H.T., Colby-Germinario S.P., Asahchop E.L., Oliveira M., McCallum M., Schader S.M., Han Y., Quan Y., Sarafianos S.G., Wainberg M.A. 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. Vol. 57, No. 7. Р. 3100–3109. doi: 10.1128/AAC.00348-13.Sluis-Cremer N., Huber K.D., Brumme C.J., Harriganb P.R. Competitive Fitness Assays Indicate that the E138A Substitution in HIV-1 Reverse Transcriptase Decreases In Vitro Susceptibility to Emtricitabine // Antimicrobial Agents and Chemotherapy. 2014. Vol. 58, No. 4. Р. 2430– 2433. doi: http://dx.doi.org/10.1128/AAC.02114-13.Sluis-Cremer N., Huber K.D., Brumme C.J., Harriganb P.R. Competitive Fitness Assays Indicate that the E138A Substitution in HIV-1 Reverse Transcriptase Decreases In Vitro Susceptibility to Emtricitabine // Antimicrobial Agents and Chemotherapy. 2014. Vol. 58, No. 4. Р. 2430– 2433. doi: http://dx.doi.org/10.1128 /AAC.02114-13.Bagella P., De Socio G.V., Ricci E., Menzaghi B., Martinelli C., Squillace N., Maggi P., Orofino G., Calza L., Carenzi L., Celesia B.M., Penco G., Di Biagio A., Valsecchi L., Vichi F., Colombo V., Parruti G., Dentone C., Falasca K., Bonfanti P., Madeddu G… Vol. C.I.S.A.I. Study Group, Italy. Durability, safety, and efficacy of rilpivirine in clinical practice: results from the SCOLTA Project // Infect Drug Resist. 2018. Vol. 11. Р. 615– 623. doi: 10.2147/IDR.S152090.Bagella P., De Socio G.V., Ricci E., Menzaghi B., Martinelli C., Squillace N., Maggi P., Orofino G., Calza L., Carenzi L., Celesia B.M., Penco G., Di Biagio A., Valsecchi L., Vichi F., Colombo V., Parruti G., Dentone C., Falasca K., Bonfanti P., Madeddu G… Vol. C.I.S.A.I. Study Group, Italy. Durability, safety, and efficacy of rilpivirine in clinical practice: results from the SCOLTA Project // Infect Drug Resist. 2018. Vol. 11. Р. 615– 623. doi: 10.2147/IDR.S152090.EACS European AIDS Clinical Society Guidelines Version 11.0 October 2021 guidelines-11.0_ru_fin_interactive.pdf (eacsociety.org). Accessed June 27, 2023.EACS European AIDS Clinical Society Guidelines Version 11.0 October 2021 guidelines-11.0_ru_fin_interactive.pdf (eacsociety.org). Accessed June 27, 2023.Клинические рекомендации. ВИЧ-инфекция у взрослых. Министерство здравоохранения Российской Федерации. 2020. Рубрикатор КР (minzdrav.gov.ru). Дата обращения от 27 июня 2023.Clinical guidelines. HIV infection in adults. Ministry of Health of Russian Federation. 2020. Accessed June 27, 2023MacBrayne C.E., Rutstein R.M., Wiznia A.A., Graham B., Alvero C.G., Fairlie L., Lypen K., George K.H., Townley E., Moye J. Jr, Costello D.G., Reding C.A., Barroso Hofer C., Crauwels H.M., Woot de Trixhe X., Tambuyzer L., Vanveggel S., Opsomer M., Kiser J.J., the IMPAACT P1090 Protocol Team. Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age // AIDS. 2021. Vol. 35, No. 9. Р. 1413–1421. doi: 10.1097/QAD.0000000000002902.MacBrayne C.E., Rutstein R.M., Wiznia A.A., Graham B., Alvero C.G., Fairlie L., Lypen K., George K.H., Townley E., Moye J. Jr, Costello D.G., Reding C.A., Barroso Hofer C., Crauwels H.M., Woot de Trixhe X., Tambuyzer L., Vanveggel S., Opsomer M., Kiser J.J., the IMPAACT P1090 Protocol Team. Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age // AIDS. 2021. Vol. 35, No. 9. Р. 1413–1421. doi: 10.1097/QAD.0000000000002902.Клинические рекомендации. ВИЧ-инфекция у детей. Министерство здравоохранения Российской Федерации. 2020. Рубрикатор КР (minzdrav.gov.ru). Дата обращения от 27 июня 2023.Clinical guidelines. HIV infection in children. Ministry of Health of Russian Federation. 2020. Accessed June 27, 2023 (In Russ.)Porter D.P., Toma J., Tan Y., Solberg O., Cai S., Kulkarni R., Andreatta K., Lie Y., Chuck S.K., Palella F., Miller M.D., White K.L. Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study // HIV Clin Trials. 2016. Vol. 17, No. 1. Р. 29–37. doi: 10.1080/15284336.2015.1115585.Porter D.P., Toma J., Tan Y., Solberg O., Cai S., Kulkarni R., Andreatta K., Lie Y., Chuck S.K., Palella F., Miller M.D., White K.L. Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study // HIV Clin Trials. 2016. Vol. 17, No. 1. Р. 29–37. doi: 10.1080/15284336.2015.1115585.Kuznetsova A., Lebedev A., Gromov K., Kazennova E., Zazzi M., Incardona F., Sönnerborg A., Bobkova M. Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients // Clin. Case Rep. 2022. Vol. 10. e05373. doi: 10.1002/ccr3.5373.Kuznetsova A., Lebedev A., Gromov K., Kazennova E., Zazzi M., Incardona F., Sönnerborg A., Bobkova M. Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients // Clin. Case Rep. 2022. Vol. 10. e05373. doi: 10.1002/ccr3.5373.Kagan R.M., Sista P., Pattery T., Bacheler L., Schwab D.A. Additional HIV-1 mutation patterns associated with reduced phenotypic susceptibility to etravirine in clinical samples // AIDS. 2009. Vol. 23, No. 12. Р. 1602–1605. doi: 10.1097/QAD.0b013e32832d8771.Kagan R.M., Sista P., Pattery T., Bacheler L., Schwab D.A. Additional HIV-1 mutation patterns associated with reduced phenotypic susceptibility to etravirine in clinical samples // AIDS. 2009. Vol. 23, No. 12. Р. 1602–1605. doi: 10.1097/QAD.0b013e32832d8771.Svarovskaia E.S., Feng J.Y., Margot N.A., Myrick F., Goodman D., Ly J.K., White K.L., Kutty N. Wang R., Borroto-Esoda K., Miller M.D. The A62V and S68G Mutations in HIV-1 Reverse Transcriptase Partially Restore the Replication Defect Associated With the K65R Mutation // J. Acquir Immune Defic. Syndr. 2008. Vol. 48, No. 4. Р. 428–436. doi: 10.1097/QAI.0b013e31817bbe93.Svarovskaia E.S., Feng J.Y., Margot N.A., Myrick F., Goodman D., Ly J.K., White K.L., Kutty N. Wang R., Borroto-Esoda K., Miller M.D. The A62V and S68G Mutations in HIV-1 Reverse Transcriptase Partially Restore the Replication Defect Associated With the K65R Mutation // J. Acquir Immune Defic. Syndr. 2008. Vol. 48, No. 4. Р. 428–436. doi: 10.1097/QAI.0b013e31817bbe93.Maldonado J.O., Mansky LM. The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations // Viruses. 2018. Vol. 10. Р. 376. doi: 10.3390/v10070376.Maldonado J.O., Mansky LM. The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations // Viruses. 2018. Vol. 10. Р. 376. doi: 10.3390/v10070376.Rhee S.Y., Varghese V., Holmes S.P., Van Zyl G.U., Steegen K., Boyd M.A., Cooper D.A., Nsanzimana S., Saravanan S., Charpentier C., de Oliveira T., Etiebet M.A., Garcia F., Goedhals D., Gomes P., Günthard H.F., Hamers R.L., Hoffmann C.J., Hunt G., Jiamsakul A., Kaleebu P., Kanki P., Kantor R., Kerschberger B., Marconi V.C,. D’amour Ndahimana J., Ndembi N., Ngo-Giang-Huong N., Rokx C., Santoro M.M., Schapiro J.M., Schmidt D., Seu L., Sigaloff K.C.E., Sirivichayakul S., Skhosana L., Sunpath H., Tang M., Yang C., Carmona S., Gupta R.K., Shafer R.W. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration // EBioMedicine. 2017. Vol. 18. Р. 225–235. http://dx.doi.org/10.1016/j.ebiom.2017.03.024.Rhee S.Y., Varghese V., Holmes S.P., Van Zyl G.U., Steegen K., Boyd M.A., Cooper D.A., Nsanzimana S., Saravanan S., Charpentier C., de Oliveira T., Etiebet M.A., Garcia F., Goedhals D., Gomes P., Günthard H.F., Hamers R.L., Hoffmann C.J., Hunt G., Jiamsakul A., Kaleebu P., Kanki P., Kantor R., Kerschberger B., Marconi V.C,. D’amour Ndahimana J., Ndembi N., Ngo-Giang-Huong N., Rokx C., Santoro M.M., Schapiro J.M., Schmidt D., Seu L., Sigaloff K.C.E., Sirivichayakul S., Skhosana L., Sunpath H., Tang M., Yang C., Carmona S., Gupta R.K., Shafer R.W. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration // EBioMedicine. 2017. Vol. 18. Р. 225–235. http://dx.doi.org/10.1016/j.ebiom.2017.03.024.Anstett K., Brenner B., Mesplede T., Wainberg M.A. HIV drug resistance against strand transfer integrase inhibitors // Retrovirology. 2017. Vol. 14. Р. 36. https://doi.org/10.1186/s12977-017-0360-7.Anstett K., Brenner B., Mesplede T., Wainberg M.A. HIV drug resistance against strand transfer integrase inhibitors // Retrovirology. 2017. Vol. 14. Р. 36. https://doi.org/10.1186/s12977-017-0360-7.Hachiya A., Kirby K.A., Ido Y., Shigemi U., Matsuda M., Okazaki R., Imamura J., Sarafianos S.G., Yokomaku Y., Iwatani Y. Impact of HIV-1 integrase L74F and V75I mutations in a clinical isolate on resistance to secondgeneration integrase strand transfer inhibitors // Antimicrob. Agents Chemother. 2017. Vol. 61: e00315–17. https://doi.org/10.1128/AAC.00315-17.Hachiya A., Kirby K.A., Ido Y., Shigemi U., Matsuda M., Okazaki R., Imamura J., Sarafianos S.G., Yokomaku Y., Iwatani Y. Impact of HIV-1 integrase L74F and V75I mutations in a clinical isolate on resistance to secondgeneration integrase strand transfer inhibitors // Antimicrob. Agents Chemother. 2017. Vol. 61: e00315–17. https://doi.org/10.1128/AAC.00315-17.Oliveira M., Ibanescu R.I., Anstett K., Mésplède T., Routy J.P., Robbins M.A., Brenner B.G., Montreal Primary HIV (PHI) Cohort Study Group. Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir // Retrovirology. 2018. Vol. 15, No. 1. Р. 56. doi: 10.1186/s12977-018-0440-3.Oliveira M., Ibanescu R.I., Anstett K., Mésplède T., Routy J.P., Robbins M.A., Brenner B.G., Montreal Primary HIV (PHI) Cohort Study Group. Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir // Retrovirology. 2018. Vol. 15, No. 1. Р. 56. doi: 10.1186/s12977-018-0440-3.Kobayashi M., Yoshinaga T., Seki T., Wakasa-Morimoto C., Brown K.W., Ferris R., Foster S.A., Hazen R.J., Miki S., Suyama-Kagitani A., Kawauchi-Miki S., Taishi T., Kawasuji T., Johns B.A., Underwood M.R., Garvey E.P., Sato A., Fujiwara T. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor // Antimicrob. Agents Chemother. 2011. Vol. 55, No. 2. Р. 813–821. doi: 10.1128/AAC.01209-10.Kobayashi M., Yoshinaga T., Seki T., Wakasa-Morimoto C., Brown K.W., Ferris R., Foster S.A., Hazen R.J., Miki S., Suyama-Kagitani A., Kawauchi-Miki S., Taishi T., Kawasuji T., Johns B.A., Underwood M.R., Garvey E.P., Sato A., Fujiwara T. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor // Antimicrob. Agents Chemother. 2011. Vol. 55, No. 2. Р. 813–821. doi: 10.1128/AAC.01209-10.Garrido C, Villacian J, Zahonero N, Pattery T, Garcia F, Gutierrez F, Caballero E, Van Houtte M, Soriano V, de Mendoza C. Vol. SINRES Group. Broad Phenotypic Cross-Resistance to Elvitegravir in HIV-Infected Patients Failing on Raltegravir-Containing Regimens // Antimicrob. Agents Chemother. 2012. Vol. 56, No. 6. Р. 2873–2878. doi: 10.1128/AAC.06170-11.Garrido C, Villacian J, Zahonero N, Pattery T, Garcia F, Gutierrez F, Caballero E, Van Houtte M, Soriano V, de Mendoza C. Vol. SINRES Group. Broad Phenotypic Cross-Resistance to Elvitegravir in HIV-Infected Patients Failing on Raltegravir-Containing Regimens // Antimicrob. Agents Chemother. 2012. Vol. 56, No. 6. Р. 2873–2878. doi: 10.1128/AAC.06170-11.Cutrell A.G., Schapiro J.M., Perno C.F., Kuritzkes D.R., Quercia R., Patel P., Polli J.W., Dorey D., Wang Y., Wu S., Van Eygen V., Crauwels H., Ford S.L., Baker M., Talarico C.L., Clair M.S., Jeffrey J., White C.T., Vanveggel S., Vandermeulen K., Margolis D.A., Aboud M., Spreen W.R., van Lunzen J. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis // AIDS. 2021. Vol. 35, No. 9. Р. 1333–1342. doi: 10.1097/QAD.0000000000002883.Cutrell A.G., Schapiro J.M., Perno C.F., Kuritzkes D.R., Quercia R., Patel P., Polli J.W., Dorey D., Wang Y., Wu S., Van Eygen V., Crauwels H., Ford S.L., Baker M., Talarico C.L., Clair M.S., Jeffrey J., White C.T., Vanveggel S., Vandermeulen K., Margolis D.A., Aboud M., Spreen W.R., van Lunzen J. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis // AIDS. 2021. Vol. 35, No. 9. Р. 1333–1342. doi: 10.1097/QAD.0000000000002883.Cabenuva. Highlights of prescribing information. CABENUVA-PI-PIL-IFU2-IFU3.PDF (gskpro.com). Accessed 22.06.2023.Cabenuva. Highlights of prescribing information. CABENUVA-PI-PIL-IFU2-IFU3.PDF (gskpro.com). Accessed 22.06.2023.Clark E., Nava B., Caputi M. Tat is a multifunctional viral protein that modulates cellular gene expression and functions // Oncotarget. 2017. Vol. 8, No. 16. Р. 27569–27581. doi: 10.18632/oncotarget.15174.Clark E., Nava B., Caputi M. Tat is a multifunctional viral protein that modulates cellular gene expression and functions // Oncotarget. 2017. Vol. 8, No. 16. Р. 27569–27581. doi: 10.18632/oncotarget.15174.Pereira E.A., da Silva L.L. HIV-1 Nef: Taking Control of Protein Trafficking // Traffic. 2016. Vol. 17(9. Р. 976–996. doi:10.1111/tra.12412.Pereira E.A., da Silva L.L. HIV-1 Nef: Taking Control of Protein Trafficking // Traffic. 2016. Vol. 17(9. Р. 976–996. doi:10.1111/tra.12412.Truman C.S., Järvelin A., Davis I., Castello A. HIV Rev-isited // Open Biol. 2020. Vol. 10. Р. 200320. https://doi.org/10.1098/rsob.200320.Truman C.S., Järvelin A., Davis I., Castello A. HIV Rev-isited // Open Biol. 2020. Vol. 10. Р. 200320. https://doi.org/10.1098/rsob.200320.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. Vol. 4. Р. 34. doi: 10.3389/fmicb.2013.00034.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. Vol. 4. Р. 34. doi: 10.3389/fmicb.2013.00034.Romani B. and Engelbrecht S. Human immunodeficiency virus type 1 Vpr: functions and molecular interactions // Journal of General Virology. 2009. Vol. 90. Р. 1795–1805. doi: 10.1099/vir.0.011726-0.Romani B. and Engelbrecht S. Human immunodeficiency virus type 1 Vpr: functions and molecular interactions // Journal of General Virology. 2009. Vol. 90. Р. 1795–1805. doi: 10.1099/vir.0.011726-0.Soper A., Juarez-Fernandez G., Aso H., Moriwaki M., Yamada E., Nakano Y., Koyanagi Y., Sato K. Various plus unique: Viral protein U as a plurifunctional protein for HIV-1 replication // Experimental Biology and Medicine. 2017. Vol. 242. Р. 850–858. doi: 10.1177/1535370217697384.Soper A., Juarez-Fernandez G., Aso H., Moriwaki M., Yamada E., Nakano Y., Koyanagi Y., Sato K. Various plus unique: Viral protein U as a plurifunctional protein for HIV-1 replication // Experimental Biology and Medicine. 2017. Vol. 242. Р. 850–858. doi: 10.1177/1535370217697384.Jin H., Sun Y., Li D., Lin M.H., Lor M., Rustanti L., Harrich D. Strong in vivo inhibition of HIV-1 replication by Nullbasic, a Tat mutant // mBio. 2019. Vol. 10. e01769–01719. doi: https://doi.org/10.1128/mBio.01769-19.Jin H., Sun Y., Li D., Lin M.H., Lor M., Rustanti L., Harrich D. Strong in vivo inhibition of HIV-1 replication by Nullbasic, a Tat mutant // mBio. 2019. Vol. 10. e01769–01719. doi: https://doi.org/10.1128/mBio.01769-19.Leoz M., Kukanja P., Luo Z., Huang F., Cary D.C., Peterlin B.M., Fujinaga K. HEXIM1-Tat chimera inhibits HIV-1 replication // PLoS Pathogens. 2018. Vol. 14. e1007402. doi: https://doi.org/10.1371/journal.ppat.1007402.Leoz M., Kukanja P., Luo Z., Huang F., Cary D.C., Peterlin B.M., Fujinaga K. HEXIM1-Tat chimera inhibits HIV-1 replication // PLoS Pathogens. 2018. Vol. 14. e1007402. doi: https://doi.org/10.1371/journal.ppat.1007402.Sgadari C., Monini P., Tripiciano A., Picconi O., Casabianca A., Orlandi C., Moretti S., Francavilla V., Arancio A., Paniccia G., Campagna M., Bellino S., Meschiari M., Nozza S., Sighinolfi L., Latini A., Muscatello A., Saracino A., Di Pietro M., Galli M., Cafaro A., Magnani M., Ensoli F., Ensoli B. 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. Vol. 10. Р. 233. doi: 10.3389/fimmu.2019.00233.Sgadari C., Monini P., Tripiciano A., Picconi O., Casabianca A., Orlandi C., Moretti S., Francavilla V., Arancio A., Paniccia G., Campagna M., Bellino S., Meschiari M., Nozza S., Sighinolfi L., Latini A., Muscatello A., Saracino A., Di Pietro M., Galli M., Cafaro A., Magnani M., Ensoli F., Ensoli B. 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. Vol. 10. Р. 233. doi: 10.3389/fimmu.2019.00233.Loret E.P., Darque A., Jouve E., Loret E.A., Nicolino-Brunet C., Morange S., Castanier E., Casanova J., Caloustian C., Bornet C., Coussirou J., Boussetta J., Couallier V., Blin O., Dussol B., Ravaux I. 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. Vol. 13. Р. 21. doi: 10.1186/s12977-016-0251-3.Loret E.P., Darque A., Jouve E., Loret E.A., Nicolino-Brunet C., Morange S., Castanier E., Casanova J., Caloustian C., Bornet C., Coussirou J., Boussetta J., Couallier V., Blin O., Dussol B., Ravaux I. 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. Vol. 13. Р. 21. doi: 10.1186/s12977-016-0251-3.Emert-Sedlak L.A., Loughran H.M., Shi H., Kulp J.L. 3rd, Shu S.T., Zhao J., Day B.W., Wrobel J.E., Reitz A.B., Smithgall T.E. Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists. Bioorg // Med. Chem. Lett. 2016. Vol. 26, No. 5. Р. 1480–1484. doi: https://doi.org/10.1016/j.bmcl.2016.01.04.Emert-Sedlak L.A., Loughran H.M., Shi H., Kulp J.L. 3rd, Shu S.T., Zhao J., Day B.W., Wrobel J.E., Reitz A.B., Smithgall T.E. Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists. Bioorg // Med. Chem. Lett. 2016. Vol. 26, No. 5. Р. 1480–1484. doi: https://doi.org/10.1016/j.bmcl.2016.01.04.Dekaban G.A. and Dikeakos J. D. HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure // AIDS Research and Therapy. 2017. Vol. 14, No. 53. doi: 10.1186/s12981-017-0175-6.Dekaban G.A. and Dikeakos J. D. HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure // AIDS Research and Therapy. 2017. Vol. 14, No. 53. doi: 10.1186/s12981-017-0175-6.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. Vol. 28, No. 6. Р. 687–698. doi: 10.2174/0929866528999201231213610.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. Vol. 28, No. 6. Р. 687–698. doi: 10.2174/0929866528999201231213610.Ruiz A. P., Ajasin D.O., Ramasamy S., DesMarais V., Eugenin E.A. and Prasad V.R. A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation // Scientific Reports. 2019. Vol. 9. Р. 3308. doi: https://doi.org/10.1038/s41598-019-39531-5.Ruiz A. P., Ajasin D.O., Ramasamy S., DesMarais V., Eugenin E.A. and Prasad V.R. A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation // Scientific Reports. 2019. Vol. 9. Р. 3308. doi: https://doi.org/10.1038/s41598-019-39531-5.Simenauer A., Nozik-Grayck E. and Cota-Gomez A. The DNA Damage Response and HIV-Associated Pulmonary Arterial Hypertension // Int. J. Mol. Sci. 2020. Vol. 21, No. 9. Р. 3305. doi: 10.3390/ijms21093305.Simenauer A., Nozik-Grayck E. and Cota-Gomez A. The DNA Damage Response and HIV-Associated Pulmonary Arterial Hypertension // Int. J. Mol. Sci. 2020. Vol. 21, No. 9. Р. 3305. doi: 10.3390/ijms21093305.Anand A.R., Rachel G. and Parthasarathy D. HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease // Front. Cardiovasc. Med. 2018. Vol. 5. Р. 185. doi: 10.3389/fcvm.2018.00185.Anand A.R., Rachel G. and Parthasarathy D. HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease // Front. Cardiovasc. Med. 2018. Vol. 5. Р. 185. doi: 10.3389/fcvm.2018.00185.Dampier W., Antell G.C., Aiamkitsumrit B., Nonnemacher M.R., Jacobson J.M., Pirrone V., Zhong W., Kercher K., Passic S., Williams J.W., James T., Devlin K.N., Giovannetti T., Libon D.J., Szep Z., Ehrlich G.D., Wigdahl B., Krebs F.C. Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status // J. Neurovirol. 2017. Vol. 23, No. 1. Р. 113–124. doi: 10.1007/s13365-016-0462-3.Dampier W., Antell G.C., Aiamkitsumrit B., Nonnemacher M.R., Jacobson J.M., Pirrone V., Zhong W., Kercher K., Passic S., Williams J.W., James T., Devlin K.N., Giovannetti T., Libon D.J., Szep Z., Ehrlich G.D., Wigdahl B., Krebs F.C. Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status // J. Neurovirol. 2017. Vol. 23, No. 1. Р. 113–124. doi: 10.1007/s13365-016-0462-3.Кузнецова А.И., Громов К.Б., Киреев Д.Е., Шлыкова А.В., Лопатухин А.Э., Казеннова Е.В., Лебедев А.В., Туманов А.С., Ким К.В., Бобкова М.Р. Анализ особенностей белка Tat вируса иммунодефицита человека 1 типа суб-субтипа А6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1) // Вопросы вирусологии. 2021. Т. 66, № 6. С. 452–463. doi: https://doi.org/10.36233/0507-4088-83.Kuznetsova A.I., Gromov K.B., Kireev D.E., Shlykova A.V., Lopatukhin A.E., Kazennova E.V., Lebedev A.V., Tumanov A.S., Kim K.V., Bobkova M.R. Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1). Problems of Virology (Voprosy Virusologii), 2021, Vol. 66, No. 6, рр. 452–463 (In Russ.) doi: https://doi.org/10.36233/0507-4088-83.de Almeida S.M., Rotta I., Vidal L.R.R., Dos Santos J.S., Nath A., Johnson K., Letendre S., Ellis R.J., H. I. V. Neurobehavioral Research Center (HNRC) Group. HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil // J. Neurovirol. 2021. Vol. 27, No. 1. Р. 126–136. doi: 10.1007/s13365-020-00935-z.de Almeida S.M., Rotta I., Vidal L.R.R., Dos Santos J.S., Nath A., Johnson K., Letendre S., Ellis R.J., H. I. V. Neurobehavioral Research Center (HNRC) Group. HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil // J. Neurovirol. 2021. Vol. 27, No. 1. Р. 126–136. doi: 10.1007/s13365-020-00935-z.Emery A., Swanstrom R. HIV-1: To Splice or Not to Splice, That Is the Question // Viruses. 2021. Vol. 13, No. 2. Р. 181. doi: 10.3390/v13020181.Emery A., Swanstrom R. HIV-1: To Splice or Not to Splice, That Is the Question // Viruses. 2021. Vol. 13, No. 2. Р. 181. doi: 10.3390/v13020181.Jackson P.E., Tebit D.M., Rekosh D., Hammarskjold M.L. Rev-RRE Functional Activity Differs Substantially Among Primary HIV-1 Isolates // AIDS Res Hum Retroviruses. 2016. Vol. 32, No. 9. Р. 923–934. doi: 10.1089/AID.2016.0047.Jackson P.E., Tebit D.M., Rekosh D., Hammarskjold M.L. Rev-RRE Functional Activity Differs Substantially Among Primary HIV-1 Isolates // AIDS Res Hum Retroviruses. 2016. Vol. 32, No. 9. Р. 923–934. doi: 10.1089/AID.2016.0047.Jackson P.E.H., Dzhivhuho G., Rekosh D., Hammarskjold M.L. Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis // Curr. HIV Res. 2020. Vol. 18, No. 2. Р. 85–98. doi: 10.2174/1570162X18666200106112842.Jackson P.E.H., Dzhivhuho G., Rekosh D., Hammarskjold M.L. Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis // Curr. HIV Res. 2020. Vol. 18, No. 2. Р. 85–98. doi: 10.2174/1570162X18666200106112842.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. Vol. 9, No. 1. Р. 5139. https://doi.org/10.1038/s41598-019-41582-7.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. Vol. 9, No. 1. Р. 5139. https://doi.org/10.1038/s41598-019-41582-7.Wang Z., Ji X., Hao Y., Hong K., Ma L., Li D., Shao Y. Premature Stop Codon at Residue 101 within HIV-1 Rev Does Not Influence Viral Replication of Clade BC but Severely Reduces Viral Fitness of Clade B // Virologica Sinica. 2020. Vol. 35. Р. 181–190. doi: https://doi.org/10.1007/s12250-019-00179-0.Wang Z., Ji X., Hao Y., Hong K., Ma L., Li D., Shao Y. Premature Stop Codon at Residue 101 within HIV-1 Rev Does Not Influence Viral Replication of Clade BC but Severely Reduces Viral Fitness of Clade B // Virologica Sinica. 2020. Vol. 35. Р. 181–190. doi: https://doi.org/10.1007/s12250-019-00179-0.Qiao X., He B., Chiu A., Knowles D.M., Chadburn A., Cerutti A. Human Immunodeficiency Virus 1 Nef Suppresses CD40-dependent Immunoglobulin Class Switching in Bystander B Cells // Nat. Immunol. 2006. Vol. 7, No. 3. Р. 302–310. doi: 10.1038/ni1302.Qiao X., He B., Chiu A., Knowles D.M., Chadburn A., Cerutti A. Human Immunodeficiency Virus 1 Nef Suppresses CD40-dependent Immunoglobulin Class Switching in Bystander B Cells // Nat. Immunol. 2006. Vol. 7, No. 3. Р. 302–310. doi: 10.1038/ni1302.Stolp B., Fackler O.T. How HIV takes advantage of the cytoskeleton in entry and replication // Viruses. 2011. Vol. 3, No. 4. Р. 293–311. doi: 10.3390/v3040293.Stolp B., Fackler O.T. How HIV takes advantage of the cytoskeleton in entry and replication // Viruses. 2011. Vol. 3, No. 4. Р. 293–311. doi: 10.3390/v3040293.Громов К.Б., Киреев Д.Е., Мурзакова А.В., Лопатухин А.Э., Казеннова Е.В., Бобкова М.Р. Анализ полиморфизма белка Nef вариантов ВИЧ-1 (Human immunodeficiency virus-1, Lentivirus, Orthoretrovirinae, Retroviridae), циркулирующих в странах бывшего СССР // Вопросы вирусологии. 2019. Т. 64, № 6. С. 281–290. doi: https://doi.org/10.36233/0507-4088-2019-64-6-281-290.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, Vol. 64, No. 6, рр. 281–290 (In Russ.) doi: https://doi.org/10.36233/0507- 4088-2019-64-6-281-290.Usami Y., Wu Y., Gottlinger H.G. SERINC3 and SERINC5 restrict HIV-1infectivity and are counteracted by Nef // Nature. 2015. Vol. 526. Р. 218–223. doi: 10.1038/nature15400.Usami Y., Wu Y., Gottlinger H.G. SERINC3 and SERINC5 restrict HIV-1infectivity and are counteracted by Nef // Nature. 2015. Vol. 526. Р. 218–223. doi: 10.1038/nature15400.Aqil M., Naqvi A.R., Bano A.S. et Jameel S., The HIV-1 Nef Protein Binds argonaute-2 and Functions as a Viral Suppressor of RNA Interference // PLoS One. 2013. No. 9. Р. e74472. doi:10.1371/journal.pone.0074472.Aqil M., Naqvi A.R., Bano A.S. et Jameel S., The HIV-1 Nef Protein Binds argonaute-2 and Functions as a Viral Suppressor of RNA Interference // PLoS One. 2013. No. 9. Р. e74472. doi:10.1371/journal.pone.0074472.Jadhav S., Makar P., Nema V. The Neuroinflammatory potential of HIV-1 Nef variants in modulating the gene expression profile of astrocytes // Cells. 2022. Vol. 11. Р. 3256. https://doi.org/10.3390/cells11203256.Jadhav S., Makar P., Nema V. The Neuroinflammatory potential of HIV-1 Nef variants in modulating the gene expression profile of astrocytes // Cells. 2022. Vol. 11. Р. 3256. https://doi.org/10.3390/ cells11203256.Almodovar S., Knight R., Allshouse A.A., Roemer S., Lozupone C., McDonald D., Widmann J., Voelkel N.F., Shelton R.J., Suarez E.B., Hammer K.W., Goujard C., Petrosillo N., Simonneau G., Hsue P.Y., Humbert M., Flores S.C. Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension // AIDS Res. Hum. Retroviruses. 2012. Vol. 28, No. 6. Р. 607–618. doi: 10.1089/AID.2011.0021.Almodovar S., Knight R., Allshouse A.A., Roemer S., Lozupone C., McDonald D., Widmann J., Voelkel N.F., Shelton R.J., Suarez E.B., Hammer K.W., Goujard C., Petrosillo N., Simonneau G., Hsue P.Y., Humbert M., Flores S.C. Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension // AIDS Res. Hum. Retroviruses. 2012. Vol. 28, No. 6. Р. 607–618. doi: 10.1089/AID.2011.0021.Kirchhoff F., Easterbrook P.J., Douglas N., Troop M., Greenough T.C., Weber J., Carl S., Sullivan J.L., Daniels R.S. Sequence variations in human immunodeficiency virus type 1 Nef are associated with different stages of disease // J. Virol. 1999. Vol. 73, No. 7. Р. 5497–5508. doi: 10.1128/JVI.73.7.5497-5508.1999.Kirchhoff F., Easterbrook P.J., Douglas N., Troop M., Greenough T.C., Weber J., Carl S., Sullivan J.L., Daniels R.S. Sequence variations in human immunodeficiency virus type 1 Nef are associated with different stages of disease // J. Virol. 1999. Vol. 73, No. 7. Р. 5497–5508. doi: 10.1128/JVI.73.7.5497-5508.1999.Das A.T., Berkhout B. How Polypurine Tract Changes in the HIV-1 RNA Genome Can Cause Resistance against the Integrase Inhibitor Dolutegravir // mBio. 2018. Vol. 9, No. 2. Р. e00006–18. doi: 10.1128/mBio.00006-18.Das A.T., Berkhout B. How Polypurine Tract Changes in the HIV-1 RNA Genome Can Cause Resistance against the Integrase Inhibitor Dolutegravir // mBio. 2018. Vol. 9, No. 2. Р. e00006–18. doi: 10.1128/mBio.00006-18.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. Vol. 13. Р. 617. https://doi.org/10.3390/v13040617.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. Vol. 13. Р. 617. https:// doi.org/10.3390/v13040617.Iwabu Y., Kinomoto M., Tatsumi M., Fujita H., Shimura M., Tanaka Y., Ishizaka Y., Nolan D., Mallal S., Sata T., Tokunaga K. Differential antiAPOBEC3G activity of HIV-1 Vif proteins derived from different subtypes // J. Biol. Chem. 2010. Vol. 285, No. 46. Р. 35350–35358. doi: 10.1074/jbc.M110.173286.Iwabu Y., Kinomoto M., Tatsumi M., Fujita H., Shimura M., Tanaka Y., Ishizaka Y., Nolan D., Mallal S., Sata T., Tokunaga K. Differential antiAPOBEC3G activity of HIV-1 Vif proteins derived from different subtypes // J. Biol. Chem. 2010. Vol. 285, No. 46. Р. 35350–35358. doi: 10.1074/jbc.M110.173286.Ronsard L., Raja R., Panwar V., Saini S., Mohankumar K., Sridharan S., Padmapriya R., Chaudhuri S., Ramachandran V.G., Banerjea A.C. Genetic and functional characterization of HIV-1 Vif on APOBEC3G degradation: First report of emergence of B/C recombinants from North India // Scientific reports. 2015. Vol. 5. Р. 15438. doi: 10.1038/srep15438.Ronsard L., Raja R., Panwar V., Saini S., Mohankumar K., Sridharan S., Padmapriya R., Chaudhuri S., Ramachandran V.G., Banerjea A.C. Genetic and functional characterization of HIV-1 Vif on APOBEC3G degradation: First report of emergence of B/C recombinants from North India // Scientific reports. 2015. Vol. 5. Р. 15438. doi: 10.1038/srep15438.

The authors declare that there are no conflicts of interest present.