Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy.

Autor:	Varco-Merth BD; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Brantley W; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Marenco A; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Duell DD; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Fachko DN; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Richardson B; Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland Ohio, USA., Busman-Sahay K; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Shao D; Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Flores W; MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, USA., Engelman K; MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, USA., Fukazawa Y; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Wong SW; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Skalsky RL; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Smedley J; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Axthelm MK; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Lifson JD; AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, Maryland, USA., Estes JD; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Edlefsen PT; Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Picker LJ; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA., Cameron CM; Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland Ohio, USA., Henrich TJ; Department of Medicine, UCSF, San Francisco, California, USA., Okoye AA; Vaccine and Gene Therapy Institute and.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2022 May 16; Vol. 132 (10).
DOI:	10.1172/JCI156063
Abstrakt:	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.
Databáze:	MEDLINE
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