Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals.
ABSTRACT: BACKGROUND:HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear. METHODS:One hundred and eight (108) biopsies from left and right colon (n?=?79) and terminal ileum (n?=?29) were collected from 19 HIV-infected and 22 HIV-uninfected participants. Levels of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA were measured by droplet digital PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6, IFN-?, IL-1?, CCL2, IL-8, and IFN-?1) was evaluated. RESULTS:Overall, CMV and EBV were detected in at least one intestinal site in 60.5 and 78.9% of participants, respectively. HIV-infected individuals demonstrated less detectable CMV (PB?=?0.02); CMV was more frequently detected in terminal ileum than colon (PB?=?0.05). Detectable EBV was more frequent among HIV-infected (P?B=?0.04) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected participants, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (P?=?0.03). Presence of CMV was associated with upregulated expression of all selected cytokines in the ileum (all P?
PROVIDER: S-EPMC5654609 | BioStudies |