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dc.contributor.authorVarco-Merth, Benjamin D
dc.contributor.authorBrantley, William
dc.contributor.authorMarenco, Alejandra
dc.contributor.authorDuell, Derick D
dc.contributor.authorFachko, Devin N
dc.contributor.authorRichardson, Brian
dc.contributor.authorBusman-Sahay, Kathleen
dc.contributor.authorShao, Danica
dc.contributor.authorFlores, Walter
dc.contributor.authorEngelman, Kathleen
dc.contributor.authorFukazawa, Yoshinori
dc.contributor.authorWong, Scott W
dc.contributor.authorSkalsky, Rebecca L
dc.contributor.authorSmedley, Jeremy
dc.contributor.authorAxthelm, Michael K
dc.contributor.authorLifson, Jeffrey D
dc.contributor.authorEstes, Jacob D
dc.contributor.authorEdlefsen, Paul T
dc.contributor.authorPicker, Louis J
dc.contributor.authorCameron, Cheryl Ma
dc.contributor.authorHenrich, Timothy J
dc.contributor.authorOkoye, Afam A
dc.date.accessioned2023-09-25T14:05:17Z
dc.date.available2023-09-25T14:05:17Z
dc.date.issued2022-05-16
dc.identifier.citationVarco-Merth BD, Brantley W, Marenco A, Duell DD, Fachko DN, Richardson B, Busman-Sahay K, Shao D, Flores W, Engelman K, Fukazawa Y, Wong SW, Skalsky RL, Smedley J, Axthelm MK, Lifson JD, Estes JD, Edlefsen PT, Picker LJ, Cameron CM, Henrich TJ, Okoye AA. Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy. J Clin Invest. 2022 May 16;132(10):e156063. doi: 10.1172/JCI156063. PMID: 35316218; PMCID: PMC9106346.en_US
dc.identifier.eissn1558-8238
dc.identifier.doi10.1172/JCI156063en_US
dc.identifier.pmid35316218
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52569
dc.description.abstractProliferation of latently infected CD4+ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4+ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA-treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4+ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.en_US
dc.language.isoenen_US
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.relation.urlhttps://doi.org/10.1172/jci156063en_US
dc.rightsCopyright: © 2022, Varco-Merth et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAIDS/HIVen_US
dc.subjectHomeostasisen_US
dc.subjectT cellsen_US
dc.titleRapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapyen_US
dc.typeJournal Articleen_US
dc.source.journaltitleThe Journal of clinical investigation
dc.source.volume132
dc.source.issue10
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalThe Journal of clinical investigation
refterms.dateFOA2023-09-25T14:05:18Z
dc.contributor.departmentMassBiologicsen_US


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Copyright: © 2022, Varco-Merth et al. This is an open access article published under
the terms of the Creative Commons Attribution 4.0 International License.
Except where otherwise noted, this item's license is described as Copyright: © 2022, Varco-Merth et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.