The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria

• DOI: 10.1371/journal.ppat.1006226
• Publication Date: 2017-02-27T18:47:29Z
• Authors: Alyson C. Yoder; Kejun Guo; Stephanie M. Dillon; Tzu Phang; Eric J. Lee; Michael S. Harper; Karen Helm; John C. Kappes; Christina Ochsenb...; Martin D. McCarter; Cara C. Wilson; Mario L. Santiago
• Keywords: Ex vivo; Granzyme; Intestinal mucosa

Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines mitogen-activated cells from peripheral blood. However, primarily targets mucosal compartments during acute infection vivo. Moreover, early causes extensive depletion of the gastrointestinal tract herald persistent inflammation due translocation enteric microbes systemic circulation. Here, we profiled primary intestinal infected ex vivo with transmitted/founder (TF) HIV-1. Infections were performed presence or absence Prevotella stercorea, a gut microbe enriched mucosa HIV-1-infected individuals enhanced both TF replication death In bacteria, triggered shutdown response involving downregulation reactome genes, while perturbing genes linked OX40, PPAR FOXO3 signaling. did not perturb these sets pathways. Instead, granzyme Th17 function, inhibited G1/S cycle checkpoint downstream microbe-exposed cells. To gain insights on differential effects, landscape HIV-1-uninfected exposed bacteria. Microbial exposure upregulated involved proliferation, MAPK activation, differentiation type I interferon Our findings reveal microbial influenced how altered transcriptome, potential consequences for susceptibility, survival inflammation. The HIV-1- microbe-altered unraveled here may serve as molecular blueprint basic