HIV-1 persistence in CD4+ T cells with stem cell–like properties

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Abstract

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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Figure 1: CD4+ TSCM cells represent a long-term reservoir for HIV-1 in HAART-treated patients.
Figure 2: Phylogenetic analysis of HIV-1 sequences isolated from CD4+ TSCM cells.

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Acknowledgements

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).

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M.J.B., X.G.Y. and M.L. came up with the research idea, study design and concept. M.J.B. and M.L. wrote the manuscript. M.J.B., H.S., E.M.-G., J.L., J.Z.L. and T.J.H. performed experiments. M.J.B., X.G.Y. and M.L. analyzed and interpreted data. F.P., B.D.W. and E.S.R. contributed peripheral blood mononuclear cell samples from biorepositories. C.L., A.S. and K.S. provided technical assistance. R.Z. and Z.O. provided biostatistical assistance. J.Z.L., T.J.H., B.D.W., E.S.R. and X.G.Y. critically reviewed the manuscript. M.L. supervised all aspects of this study, including design, execution, interpretation and manuscript preparation.

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Correspondence to Mathias Lichterfeld.

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The authors declare no competing financial interests.

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Supplementary Figures 1–9 and Supplementary Table 1 (PDF 10620 kb)

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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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