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

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 and mitogen-activated cd4+ t cells from peripheral blood. however,hiv-1 primarily targets mucosal compartments during acute infection in vivo. moreover,early hiv-1 infection causes extensive depletion of cd4+ t cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. here,we profiled the transcriptome of primary intestinal cd4+ t cells infected ex vivo with transmitted/founder (tf) hiv-1. infections were performed in the presence or absence of prevotella stercorea,a gut microbe enriched in the mucosa of hiv-1-infected individuals that enhanced both tf hiv-1 replication and cd4+ t cell death ex vivo. in the absence of bacteria,hiv-1 triggered a cellular shutdown response involving the downregulation of hiv-1 reactome genes,while perturbing genes linked to ox40,ppar and foxo3 signaling. however,in the presence of bacteria,hiv-1 did not perturb these gene sets or pathways. instead,hiv-1 enhanced granzyme expression and th17 cell function,inhibited g1/s cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut cd4+ t cells. to gain insights on these differential effects,we profiled the gene expression landscape of hiv-1-uninfected gut cd4+ t cells exposed to bacteria. microbial exposure upregulated genes involved in cellular proliferation,mapk activation,th17 cell differentiation and type i interferon signaling. our findings reveal that microbial exposure influenced how hiv-1 altered the gut cd4+ t cell transcriptome,with potential consequences for hiv-1 susceptibility,cell survival and inflammation. the hiv-1- and microbe-altered pathways unraveled here may serve as a molecular blueprint to gain basic insights in mucosal hiv-1 pathogenesis. © 2017 yoder et al.