Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones.

Immunity 2022 Jun 14

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Understanding the drivers and markers of clonally expanding HIV-1-infected CD4+ T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, which captures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequences within the same single cell to track clonal expansion dynamics in longitudinally archived samples from six HIV-1-infected individuals (during viremia and after suppressive antiretroviral therapy) and two uninfected individuals, in unstimulated conditions and after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistent antigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1-polarized, antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA+ T cell clones were larger in clone size, established during viremia, persistent after viral suppression, and enriched in GZMB+ cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4+ T cells and drivers of clonal expansion provides another direction for HIV-1 eradication. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Jack A Collora, Runxia Liu, Delia Pinto-Santini, Neal Ravindra, Carmela Ganoza, Javier R Lama, Ricardo Alfaro, Jennifer Chiarella, Serena Spudich, Karam Mounzer, Pablo Tebas, Luis J Montaner, David van Dijk, Ann Duerr, Ya-Chi Ho. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity. 2022 Jun 14;55(6):1013-1031.e7