Bibliographic Details
| Title: |
Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus-infected rhesus macaques on antiretroviral therapy. |
| Authors: |
Varco-Merth, Benjamin D., Brantley, William, Marenco, Alejandra, Duell, Derick D., Fachko, Devin N., Richardson, Brian, Busman-Sahay, Kathleen, Shao, Danica, Flores, Walter, Engelman, Kathleen, Yoshinori Fukazawa, Wong, Scott W., Skalsky, Rebecca L., Smedley, Jeremy, Axthelm, Michael K., Lifson, Jeffrey D., Estes, Jacob D., Edlefsen, Paul T., Picker, Louis J., Cameron, Cheryl M. A. |
| Source: |
Journal of Clinical Investigation. 5/16/2022, Vol. 132 Issue 10, p1-15. 15p. |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Health Source: Nursing/Academic Edition |
