| Literature DB >> 35320704 |
Jack A Collora1, Runxia Liu1, Delia Pinto-Santini2, Neal Ravindra3, Carmela Ganoza4, Javier R Lama4, Ricardo Alfaro5, Jennifer Chiarella6, Serena Spudich6, Karam Mounzer7, Pablo Tebas8, Luis J Montaner9, David van Dijk3, Ann Duerr2, Ya-Chi Ho10.
Abstract
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.Entities:
Keywords: HIV-1 latent reservoir; HIV-1 persistence; HIV-1-induced immune dysfunction; T cell expansion dynamics; TNF response; antigen stimulation; clonal expansion; cytotoxic CD4(+) T lymphocytes; granzyme B; single-cell RNA-seq
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Year: 2022 PMID： 35320704 PMCID： PMC9203927 DOI： 10.1016/j.immuni.2022.03.004
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474