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
| Autor: | Mette Nyegaard, Karen Jang, Xutao Deng, Amirali Afshari, Kara Marson, Young Kim, Nadia R. Roan, Philip J. Norris, Satish K. Pillai, Ali Danesh, Heather C. Inglis, Christopher D. Pilcher, Erika G Marques de Menezes, Jason Neidleman, Jean-Noel Billaud, Ashley F. George |
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| Přispěvatelé: | Silvestri, Guido |
| Rok vydání: | 2020 |
| Předmět: |
Male
HIV Infections Medical and Health Sciences Transcriptome Cohort Studies 0302 clinical medicine 2.1 Biological and endogenous factors Aetiology 0303 health sciences human immunodeficiency virus Extracellular vesicle Genitalia Female Biological Sciences Phenotype miRNAs HIV/AIDS Cytokines Female transcription Infection Biotechnology Adult Stromal cell Sexual Behavior Immunology Semen Biology Microbiology Proinflammatory cytokine 03 medical and health sciences Extracellular Vesicles Viral entry Clinical Research Virology microRNA stromal fibroblasts Genetics Humans Genitalia 030304 developmental biology Agricultural and Veterinary Sciences Prevention female reproductive tract epithelial cells MicroRNAs Good Health and Well Being Insect Science seminal plasma HIV-1 Pathogenesis and Immunity 030215 immunology |
| Zdroj: | J Virol Journal of virology, vol 94, iss 16 Marques de Menezes, E G, Jang, K, George, A F, Nyegaard, M, Neidleman, J, Inglis, H C, Danesh, A, Deng, X, Afshari, A, Kim, Y H, Billaud, J-N, Marson, K, Pilcher, C D, Pillai, S K, Norris, P J & Roan, N R 2020, ' 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 ', Journal of Virology, vol. 94, no. 16, e00525-20 . https://doi.org/10.1128/JVI.00525-20 |
| ISSN: | 1098-5514 |
| Popis: | 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. 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 its associated EVs elicit potent proinflammatory transcriptional responses in cells that line the genital tract. EVs from HIV-infected men exhibit a more diverse repertoire of miRNAs than EVs from uninfected men. Our findings suggest that EVs from the semen of HIV-infected men may significantly impact the likelihood of HIV transmission through multiple mechanisms. |
| Databáze: | OpenAIRE |
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