{"doi":"10.1172/jci156063","title":"Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus–infected rhesus macaques on antiretroviral therapy","abstract":"Proliferation 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.","journal":"Journal of Clinical Investigation","year":2022,"id":256209,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":708414,"name":"William Brantley","orcid":null,"position":1,"is_corresponding":false},{"id":685751,"name":"Alejandra Marenco","orcid":null,"position":2,"is_corresponding":false},{"id":685749,"name":"Derick D. 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Skalsky","orcid":"0000-0003-2967-9478","position":12,"is_corresponding":false},{"id":344045,"name":"Jeremy Smedley","orcid":"0000-0003-3369-4662","position":13,"is_corresponding":false},{"id":263668,"name":"Michael K. Axthelm","orcid":"0000-0002-1984-5906","position":14,"is_corresponding":false},{"id":233484,"name":"Jeffrey D. Lifson","orcid":"0000-0002-9494-0268","position":15,"is_corresponding":false},{"id":95245,"name":"Jacob D. Estes","orcid":"0000-0002-9652-6394","position":16,"is_corresponding":false},{"id":472908,"name":"Paul T. Edlefsen","orcid":"0000-0002-8393-8103","position":17,"is_corresponding":false},{"id":246463,"name":"Louis J. Picker","orcid":"0000-0003-0546-398X","position":18,"is_corresponding":false},{"id":105517,"name":"Cheryl Cameron","orcid":"0000-0002-0574-3781","position":19,"is_corresponding":false},{"id":239686,"name":"Timothy J. Henrich","orcid":"0000-0002-6684-0622","position":20,"is_corresponding":false},{"id":277149,"name":"Afam A. 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