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bioRxiv · 10.1101/2022.03.02.482683

Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses

Weymar, G. H.·Bar-On, Y.·Oliveira, T. Y.·Gaebler, C.·Ramos, V.·Hartweger, H.·Breton, G.·Caskey, M.·Cohn, L. B.·Jankovic, M.·Nussenzweig, M. C.
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Abstract

Antiretroviral therapy controls but does not cure HIV-1 infection due to a reservoir of rare CD4+ T cells harboring latent proviruses. Little is known about the transcriptional program of latent cells. Here we report a novel strategy to enrich clones of latent cells carrying intact, replication- competent HIV-1 proviruses from blood based on their expression of unique T cell receptors. Latent cell enrichment enabled single cell transcriptomic analysis of 1,050 CD4+ T cells belonging to expanded clones harboring intact HIV-1 proviruses from 6 different individuals. The analysis revealed that most of these cells are T effector memory cells that are enriched for expression of HLA-DR, HLA-DP, CD74, CCL5, Granzymes A and K, cystatin F, LYAR and DUSP2. We conclude that expanded clones of latent cells carrying intact HIV-1 proviruses persist preferentially in a distinct CD4+ T cell population opening new possibilities for eradication. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/482683v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@19e89d2org.highwire.dtl.DTLVardef@16a5685org.highwire.dtl.DTLVardef@563a97org.highwire.dtl.DTLVardef@120a224_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Weymar, G. H., Bar-On, Y., Oliveira, T. Y., Gaebler, C., Ramos, V., Hartweger, H., Breton, G., Caskey, M., Cohn, L. B., Jankovic, M., Nussenzweig, M. C.. 2022-03-02. Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses. https://doi.org/10.1101/2022.03.02.482683

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