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

Author:

Marques de Menezes Erika G.12ORCID,Jang Karen34,George Ashley F.34,Nyegaard Mette5,Neidleman Jason34,Inglis Heather C.1,Danesh Ali1,Deng Xutao1,Afshari Amirali6,Kim Young H.7,Billaud Jean-Noël8,Marson Kara9,Pilcher Christopher D.9,Pillai Satish K.12,Norris Philip J.1210,Roan Nadia R.34

Affiliation:

1. Vitalant Research Institute, San Francisco, California, USA

2. Department of Laboratory Medicine, University of California, San Francisco, California, USA

3. Gladstone Institute of Virology and Immunology, San Francisco, California, USA

4. Department of Urology, University of California, San Francisco, California, USA

5. Department of Biomedicine, Aarhus University, Aarhus, Denmark

6. System Biosciences, Inc., Palo Alto, California, USA

7. Agilent Technologies, Inc., Santa Clara, California, USA

8. Qiagen Bioinformatics, Redwood City, California, USA

9. Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA

10. Department of Medicine, University of California, San Francisco, California, USA

Abstract

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.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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