Effect of rhesus cytomegalovirus (RhCMV) infection or RhCMV-based vaccine administration on gut microbiome of rhesus macaques

Both the gut microbiota and chronic latent viral infections have profound effects on the host immune system, but interactions between these two influences is unknownhave been only superficially explored. Cytomegalovirus (CMV), for example, infects 50-90% of adult humans and drives significant changes in immune-cell phenotypes and functions. Similarly, certain members of the commensal gut microbial community affect T-cell development in mice and non-human primates. It is unknown if changes imposed by CMV on the host intestinal microbiome contribute to immunologic effects of the infection. Here we show that rhesus cytomegalovirus (RhCMV) infection in rhesus macaques housed outdoors is associated with specific differences in gut microbiota composition, including decreased abundance of Firmicutes. The extent of change in differentially abundant taxa was associated with overarching immunologic changes also associated with RhCMV infection, most significantly the proliferation, differentiation, and cytokine production of CD8+ T cells. Furthermore, RhCMV infection disrupted the relationship between short-chain fatty acid producers and Treg/Th17 balance associations observed in seronegative animals between specific bacterial taxa in the gut and circulating immune-cell phenotypes, most prominently the relationship between short-chain fatty acid (SCFA) producers and Treg/Th17 balance, suggesting that some immunologic effects of CMV are due to disruption of previously existing host-microbe relationships. CMV is therefore an important modifier of the relationships between gut microbes and host immunity.