The continuing spread of HIV/AIDS is predominantly fueled by sexual
exposure to HIV-contaminated semen. Seminal plasma (SP), the liquid portion of semen, harbors a variety of factors that may favor HIV transmission by facilitating viral
entry into host cells, eliciting the production of proinflammatory cytokines, and enhancing the translocation of HIV across the genital epithelium. One important and
abundant class of factors in SP is extracellular vesicles (EVs), which, in general, are
important 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 interface
with the luminal contents of the female reproductive tract. Semen EV fractions from
acutely infected individuals induced a more proinflammatory signature than those
from uninfected individuals. This was not associated with any observable differences
in the surface phenotypes of the vesicles. However, microRNA (miRNA) expression
profiling analysis revealed that EV fractions from infected individuals exhibit a
broader and more diverse profile than those from uninfected individuals. Taken together, our data suggest that SP EVs from HIV-infected individuals exhibit unique
miRNA signatures and exert potent proinflammatory transcriptional changes in cells
of the female reproductive tract, which may facilitate HIV transmission. Less...