Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract

Erika G Marques de Menezes, Karen Jang, Ashley F George, Mette Nyegaard, Jason Neidleman, Heather C Inglis, Ali Danesh, Xutao Deng, Amirali Afshari, Young H Kim, Jean-Noël Billaud, Kara Marson, Christopher D Pilcher, Satish K Pillai, Philip J Norris, Nadia R Roan

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11 Citations (Scopus)

Abstract

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 pro-inflammatory 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 semen of HIV-infected individuals. We report here that fractionated SP enriched for EVs from HIV-infected men induce potent transcriptional responses in epithelial and stromal cells that interface with luminal contents of the female reproductive tract. Compared to semen EV fractions from uninfected individuals, those from acutely-infected individuals induced a more pro-inflammatory signature. This was not associated with any observable differences in the surface phenotypes of the vesicles. However, miRNA expression profiling analysis revealed that EV fractions from infected individuals exhibit a broader and more diverse profile. Taken together, our data suggest that SP EVs from HIV-infected individuals exhibit unique miRNA signatures and exert potent pro-inflammatory transcriptional changes in cells of the female reproductive tract, which may facilitate HIV transmission.IMPORTANCE Seminal plasma (SP), the major vehicle for HIV, can modulate HIV transmission risk through a variety of mechanisms. Extracellular vesicles (EVs) are extremely abundant in semen, and because they play a key role in intercellular communication pathways and immune regulation, they may impact the likelihood of HIV transmission. However, little is known about the properties and signaling effects of SP-derived EVs in the context of HIV transmission. Here, we conduct a phenotypic, transcriptomic, and functional characterization of SP and SP-derived EVs from uninfected and HIV-infected men. We find that both SP and their associated EVs elicit potent pro-inflammatory transcriptional response in cells that line the genital tract. Compared to EVs from uninfected men, those from HIV-infected men exhibit a more diverse repertoire of miRNAs. Our findings suggest that EVs from semen of HIV-infected men may significantly impact the likelihood of HIV transmission through multiple mechanisms.

Original languageEnglish
Article numbere00525-20
JournalJournal of Virology
Volume94
Issue number16
Number of pages21
ISSN0022-538X
DOIs
Publication statusPublished - Aug 2020
Externally publishedYes

Bibliographical note

Copyright © 2020 American Society for Microbiology.

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