biostudies-literaturePeterson JJNIDDK NIH HHSNIAID NIH HHSNIAIDe196536https://www.ebi.ac.uk/biostudies/studies/S-EPMC12904708biostudies-literatureUnknown136(4)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 infecThe Journal of clinical investigationSingle-cell characterization of the gastrointestinal HIV reservoir reveals heterogeneous cellular phenotypes.PMC12904708UM1 AI164567R01AI143381NIAID #5- UM1AI164567R01 DK131526NIAID #5-R01AI143381UM1AI164567R01 AI143381NIDDK 1R01DK131526Bennett ESPeery AFArchin NMPeterson JJBaker CChandel SJames KWhitaker TWhite CHAllard BMargolis DMClohosey MBrowne EPPedersen SBetts MRGay CLWu VfalseSingle-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 infec2026-01-01T00:00:00Z2026 Feb2026-07-15T21:56:58.879Z2026-07-09T13:09:12.971ZS-EPMC129047084143312410.1172/JCI196536