{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T22:16:15Z","timestamp":1740176175973,"version":"3.37.3"},"reference-count":23,"publisher":"Central Research Institute for Epidemiology","issue":"5","license":[{"start":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T00:00:00Z","timestamp":1731110400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["virusjour.crie.ru"],"crossmark-restriction":false},"short-container-title":["Problems of Virology"],"abstract":"<jats:p>Introduction. Chemotherapy of HIV infection remains the only means of treating the disease. The process of development new and improving previously developed drugs is therefore considered a priority. One of the preclinical stage of drug efficacy testing is research in the virus-cell model system in vitro.\r\nThe aim. To evaluate the antiviral efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) 6HP and 3TC during HIV-1 replication in the neoplastic MT-4 cell line.\r\nMaterials and methods. Two variants of the CD4+ T-lymphocyte MT-4 cell line (MT-4\/1 and MT-4\/2) transformed by Human T-lymphotropic virus type 1 (Retroviridae: Orthoretrovirinae: Deltaretrovirus: HTLV-1), with different levels of HIV-1 replication were used. Drugs ammonium-3\u2019-azido-3\u2019-deoxythymidine-5\u2019-carbomoylphosphonat (6HP) and 2\u2019,3\u2019-dideoxy-3\u2019-thiacytidine (3TC) were used to suppress the virus.\r\nResults and discussion. The replication activity of HIV-1 was observed to be higher in the MT-4\/2 line than in the MT-4\/1 line for different strains of the virus. The use of each of the substances separately showed a more significant inhibition of viral activity in MT-4\/1 than in MT-4\/2 cells. When used together, the inhibition level was almost the same in all cases and ranged from 87\u201296% for the MT-4\/1 line and 83\u201289% for the MT-4\/2 line. High efficacy was observed when using lower concentrations of drugs compared to individual use.\r\nConclusion. The combined use of NRTIs 6\u041d\u0420 and 3T\u0421 is promising for the treatment of HIV-infected patients at different stages of infection and with different levels of viral load.<\/jats:p>","DOI":"10.36233\/0507-4088-247","type":"journal-article","created":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T21:06:56Z","timestamp":1731186416000},"page":"441-448","update-policy":"https:\/\/doi.org\/10.36233\/0372-9311-crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of anti-HIV-1 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus type 1) activity of 6HP and 3TC in vitro using MT-4 cell line variants with different replicative activity"],"prefix":"10.36233","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2702-8578","authenticated-orcid":false,"given":"Lyudmila B.","family":"Kalnina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-770X","authenticated-orcid":false,"given":"Lyudmila M.","family":"Selimova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-5671","authenticated-orcid":false,"given":"Dmitry N.","family":"Nosik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"22004","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"doi-asserted-by":"publisher","key":"ref1","DOI":"10.36233\/0372-9311-345"},{"doi-asserted-by":"crossref","unstructured":"Ndung\u2019u T., McCune J.M., Deeks S.G. Why and where an HIV cure is needed and how it might be achieved. Nature. 2019; 576(7787): 397\u2013405. https:\/\/doi.org\/10.1038\/s41586-019-1841-8","key":"ref2","DOI":"10.1038\/s41586-019-1841-8"},{"doi-asserted-by":"crossref","unstructured":"Men\u00e9ndez-Arias L., Sebasti\u00e1n-Mart\u00edn A., \u00c1lvarez M. Viral reverse transcriptases. Virus Res. 2017; 234: 153\u201376. https:\/\/doi.org\/10.1016\/j.virusres.2016.12.019","key":"ref3","DOI":"10.1016\/j.virusres.2016.12.019"},{"doi-asserted-by":"crossref","unstructured":"Mitsuya H., Weinhold K.J., Furman P.A., St Clair M.H., Lehrman S.N., Gallo R.C., et al. 3\u2019-azido-3\u2019-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III\/lymphadenopathy-associated virus in vitro. Proc. Natl Acad. Sci. USA. 1985; 82(20): 7096\u2013100. https:\/\/doi.org\/10.1073\/pnas.82.20.7096","key":"ref4","DOI":"10.1073\/pnas.82.20.7096"},{"doi-asserted-by":"crossref","unstructured":"Men\u00e9ndez-Arias L. Molecular basis of human immunodeficiency virus type 1 drug resistance: overview and recent developments. Antiviral Res. 2013; 98(1): 93\u2013120. https:\/\/doi.org\/10.1016\/j.antiviral.2013.01.007.","key":"ref5","DOI":"10.1016\/j.antiviral.2013.01.007"},{"doi-asserted-by":"crossref","unstructured":"Khandazhinskaya \u0410.L., Shirokova E.A. AZT 5\u2019-Phosphonates: achievements and trends in the treatment and prevention of Hiv infection. Acta Naturae. 2013; 5(3): 54\u201361. https:\/\/elibrary.ru\/rvzyvv","key":"ref6","DOI":"10.32607\/20758251-2013-5-3-54-61"},{"doi-asserted-by":"crossref","unstructured":"Galegov G.A.1, Andronova V.L. AntiHIV\/AIDS drug 6HP: antiviral activity, pre-clinical study. Efficiency in adult HIV-infected patients. 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Alteration of intracellular potassium and sodium concentrations with induction of cytopathic effects by human immunodeficiency virus. J. Virol. 1996; 70(8): 5447\u201354. https:\/\/doi.org\/10.1128\/JVI.70.8.5447-5454.1996","key":"ref19","DOI":"10.1128\/jvi.70.8.5447-5454.1996"},{"doi-asserted-by":"crossref","unstructured":"Esensten J.H., Helou Y.A., Chopra G., Weiss A., Bluestone J.A. CD28 costimulation: from mechanism to therapy. Immunity. 2016; 44(5): 973\u201388. https:\/\/doi.org\/10.1016\/j.immuni.2016.04.020","key":"ref20","DOI":"10.1016\/j.immuni.2016.04.020"},{"doi-asserted-by":"crossref","unstructured":"Sakamoto Y., Ishida T., Masaki A., Takeshita M., Iwasaki H., Yonekura K., et al. Clinical significance of CD28 gene-related activating alterations in adult T-cell leukaemia\/lymphoma. Br. J. 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