Single-cell epigenetic, transcriptional, protein, and TCR states of HIV-1-infected cells in gut

Tissue resident memory T cells (TRMs) are essential to mucosal immunity. We postulate that their long-lived tissue residency and restricted effector function promote HIV-1 persistence in human gut. We coupled single-cell-DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptor, HIV-1 DNA, and HIV-1 RNA in gut CD4+ and CD8+ T cells from ten aviremic HIV-1+ individuals and five HIV-1- donors. We found that BACH2, a transcription repressor that establishes long-lived memory in T cells, is the leading transcription factor that shapes gut TRMs into long-lived memory and restrains interferon-driven effector function.