Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures

The continuing spread of HIV/AIDS is predominantly fueled by sexualexposure to HIV-contaminated semen. Seminal plasma (SP), the liquid portion of semen, harbors a variety of factors that may favor HIV transmission by facilitating viralentry into host cells, eliciting the production of proinflammatory cytokines, and enhancing the translocation of HIV across the genital epithelium. One important andabundant class of factors in SP is extracellular vesicles (EVs), which, in general, areimportant intercellular signal transducers. Although numerous studies have characterized blood plasma-derived EVs from both uninfected and HIV-infected individuals, little is known about the properties of EVs from the semen of HIV-infected individuals. We report here that fractionated SP enriched for EVs from HIV-infected men induces potent transcriptional responses in epithelial and stromal cells that interfacewith the luminal contents of the female reproductive tract. Semen EV fractions fromacutely infected individuals induced a more proinflammatory signature than thosefrom uninfected individuals. This was not associated with any observable differencesin the surface phenotypes of the vesicles. However, microRNA (miRNA) expressionprofiling analysis revealed that EV fractions from infected individuals exhibit abroader and more diverse profile than those from uninfected individuals. Taken together, our data suggest that SP EVs from HIV-infected individuals exhibit uniquemiRNA signatures and exert potent proinflammatory transcriptional changes in cellsof the female reproductive tract, which may facilitate HIV transmission.