Luminal microvesicles uniquely influence translocating bacteria after SIV infection.

ABSTRACT

Microbial translocation contributes to persistent inflammation in both treated and untreated HIV infection. Although translocation is due in part to a disintegration of the intestinal epithelial barrier, there is a bias towards the translocation of Proteobacteria. We hypothesized that intestinal epithelial microvesicle cargo differs after HIV infection and contributes to biased translocation. We isolated gastrointestinal luminal microvesicles before and after progressive simian immunodeficiency virus (SIV) infection in rhesus macaques and measured miRNA and antimicrobial peptide content. We demonstrate that these microvesicles display decreased miR-28-5p, -484, -584-3p, and -584-5p, and let-7b-3p, as well as increased beta-defensin 1 after SIV infection. We further observed dose-dependent growth sensitivity of commensal Lactobacillus salivarius upon co-culture with isolated microvesicles. Infection-associated microvesicle differences were not mirrored in non-progressively SIV-infected sooty mangabeys. Our findings describe novel alterations of antimicrobial control after progressive SIV infection that influence the growth of translocating bacterial taxa. These studies may lead to the development of novel therapeutics for treating chronic HIV infection, microbial translocation, and inflammation.