Document Type
Article
Peer Reviewed
1
Publication Date
1-1-2014
NLM Title Abbreviation
Retrovirology
Journal/Book/Conference Title
Retrovirology
PubMed ID
25407601
DOI of Published Version
10.1186/s12977-014-0102-z
Start Page
102
Abstract
Background Exosomes are membranous nanovesicles secreted into the extracellular milieu by diverse cell types. Exosomes facilitate intercellular communication, modulate cellular pheno/genotype, and regulate microbial pathogenesis. Although human semen contains exosomes, their role in regulating infection with viruses that are sexually transmitted remains unknown. In this study, we used semen exosomes purified from healthy human donors to evaluate the role of exosomes on the infectivity of different strains of HIV-1 in a variety of cell lines. Results We show that human semen contains a heterologous population of exosomes, enriched in mRNA encoding tetraspanin exosomal markers and various antiviral factors. Semen exosomes are internalized by recipient cells and upon internalization, inhibit replication of a broad array of HIV-1 strains. Remarkably, the anti-HIV-1 activity of semen exosomes is specific to retroviruses because semen exosomes blocked replication of the murine AIDS (mAIDS) virus complex (LP-BM5). However, exosomes from blood had no effect on HIV-1 or LP-BM5 replication. Additionally, semen and blood exosomes had no effect on replication of herpes simplex virus; types 1 and 2 (HSV1 and HSV2). Mechanistic studies indicate that semen exosomes exert a post-entry block on HIV-1 replication by orchestrating deleterious effects on particle-associated reverse transcriptase activity and infectivity. Conclusions These illuminating findings i) improve our knowledge of the cargo of semen exosomes, ii) reveal that semen exosomes possess anti-retroviral activity, and iii) suggest that semen exosome-mediated inhibition of HIV-1 replication may provide novel opportunities for the development of new therapeutics for HIV-1.
Keywords
OAfund, Exosome, Semen, HIV-1, mAIDS, HSV
Journal Article Version
Version of Record
Published Article/Book Citation
Retrovirology 2014, 11:102 doi:10.1186/s12977-014-0102-z
Rights
Copyright: © 2014 Madison et al.; licensee BioMed Central Ltd. Posted by permission.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
URL
https://ir.uiowa.edu/microbiology_pubs/1