Exosomes in human semen restrict HIV-1 transmission by vaginal cells and block intravaginal replication of LP-BM5 murine AIDS virus complex

Abstract

Exosomes are membranous extracellular nanovesicles secreted by diverse cell types. Exosomes from healthy human semen have been shown to inhibit HIV-1 replication and to impair progeny virus infectivity. In this study, we examined the ability of healthy human semen exosomes to restrict HIV-1 and LP-BM5 murine AIDS virus transmission in three different model systems. We show that vaginal cells internalize exosomes with concomitant transfer of functional mRNA. Semen exosomes blocked the spread of HIV-1 from vaginal epithelial cells to target cells in our cell-to-cell infection model and suppressed transmission of HIV-1 across the vaginal epithelial barrier in our trans-well model. Our in vivo model shows that human semen exosomes restrict intravaginal transmission and propagation of murine AIDS virus. Our study highlights an antiretroviral role for semen exosomes that may be harnessed for the development of novel therapeutic strategies to combat HIV-1 transmission.

Effect of prolonged freezing of semen on exosome recovery and biologic activity

“…Following isolation, we examined SE concentration by measuring the protein content of intact SE using Bradford assay12. We found that SE concentration ranged between 5.55 μg/μl to 6.37 μg/μl.…”

“…Semen exosomes (SE) enwrap various RNA (micro RNA [miRNA] and messenger RNA [mRNA]) and protein cargos1234. Exosomal proteins such as tetraspanins (CD9, CD63, and CD81) are commonly used as markers of exosome15.…”

“…The protein and RNA content of SE have the potential to be used as intercellular messengers, biomarkers, or therapeutic tools for reproductive disorders and sexually transmitted diseases6. Indeed, previous studies have found that SE contain inhibitory molecules that restrict retroviral infection, including infection with MLV and HIV-1 in cultured cells12 and in a mouse model of retroviral infection2.…”

“…While short-time freezing of semen does not affect SE function such as anti-HIV activity12, the effect of prolonged freezing on SE recovery, and biological activity is unknown. Furthermore, the effect of donor illicit drug use on SE characteristics is not known.…”

Exosomes in semen: opportunities as a new tool in prostate cancer diagnosis

“…In this common cancer, semen is responsible of HPV delivery and caused the continuous exposure of the cervix to immunesuppressive agents. The correlation between SE, immunity and HIV-1 transmission have been demonstrated (22). SE may either enhance or block replication of sexually transmitted pathogens, such as HIV-1 (19,20).…”