Single-cell characterization of the gastrointestinal HIV reservoir reveals heterogeneous cellular phenotypes

Human gastrointestinal (GI) tissues are a major site of HIV-1 viral persistence, but the nature of the GI reservoir remains poorly described. To characterize the GI HIV reservoir, we profiled cells from GI tissue and matched PBMCs from 10 people with HIV on antiretroviral therapy using single-cell RNA sequencing. We identified distinct compartment-specific patterns of gene expression, highlighting key differences between blood and colon CD4+ T cell populations. vRNA+ cells from both blood and GI tissue were heterogeneous and found in multiple subtypes of CD4+ T cells, although vRNA+ cells were particularly enriched in cells with Th17 or Treg17 phenotypes. Transcriptomic comparison of HIV vRNA+ and vRNA- T cells revealed 116 differentially expressed genes that were associated with HIV infection, including ZBED2, MAF, and IL17F. These data provide what we believe to be new information regarding the GI-resident HIV reservoir and suggest that compartment-specific patterns of gene expression are associated with HIV infection.