Cellular HIV-1 reservoirs that persist despite antiretroviral treatment are incompletely defined. We show that during suppressive antiretroviral therapy, CD4+ T memory stem cells (TSCM cells) harbor high per-cell levels of HIV-1 DNA and make increasing contributions to the total viral CD4+ T cell reservoir over time. Moreover, we conducted phylogenetic studies that suggested long-term persistence of viral quasispecies in CD4+ TSCM cells. Thus, HIV-1 may exploit the stem cell characteristics of cellular immune memory to promote long-term viral persistence.
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This work was supported by the American Foundation for AIDS Research (grant 108302-51-RGRL to M.L.) and by the US National Institutes of Health (grants AI098487 and AI106468 to M.L., AI089339 to X.G.Y., AI098480 to T.J.H. and AI100699 to J.Z.L.). M.L. is a recipient of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant number 2009034). M.J.B. is supported by a fellowship award from the European Molecular Biology Laboratory and by the Tosteson postdoctoral fellowship award from Massachusetts General Hospital. Patient blood sample collection was supported by the US National Institutes of Health (grant AI074415), by the Mark and Lisa Schwartz Foundation and by the Bill & Melinda Gates Foundation. Chronically infected 293T cells were kindly provided by F. Bushman (University of Pennsylvania). HIV-1 isolates were kindly provided by D. Littman (New York University).
The authors declare no competing financial interests.
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Buzon, M., Sun, H., Li, C. et al. HIV-1 persistence in CD4+ T cells with stem cell–like properties. Nat Med 20, 139–142 (2014). https://doi.org/10.1038/nm.3445
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