AUTHOR=Costantini Paolo E. , Vanpouille Christophe , Firrincieli Andrea , Cappelletti Martina , Margolis Leonid , Ñahui Palomino Rogers A. 

TITLE=Extracellular Vesicles Generated by Gram-Positive Bacteria Protect Human Tissues Ex Vivo From HIV-1 Infection

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.822882

DOI=10.3389/fcimb.2021.822882

ISSN=2235-2988

ABSTRACT=<p>Vaginal microbiota dominated by lactobacilli protects women from sexually transmitted infection, in particular HIV-1. This protection is, in part, mediated by <italic>Lactobacillus</italic>-released extracellular vesicles (EVs). Here, we investigated whether EVs derived from other Gram-positive bacteria also present in healthy vaginas, in particular <italic>Staphylococcus aureus</italic>, <italic>Gardnerella vaginalis</italic>, <italic>Enterococcus faecium</italic>, and <italic>Enterococcus faecalis</italic>, can affect vaginal HIV-1 infection. We found that EVs released by these bacteria protect human cervico-vaginal tissues <italic>ex vivo</italic> and isolated cells from HIV-1 infection by inhibiting HIV-1-cell receptor interactions. This inhibition was associated with a diminished exposure of viral Env by steric hindrance of gp120 or gp120 modification evidenced by the failure of EV-treated virions to bind to nanoparticle-coupled anti-Env antibodies. Furthermore, we found that protein components associated with EV’s outer surface are critical for EV-mediated protection from HIV-1 infection since treatment of bacteria-released EVs with proteinase K abolished their anti-HIV-1 effect. We identified numerous EV-associated proteins that may be involved in this protection. The identification of EVs with specific proteins that suppress HIV-1 may lead to the development of novel strategies for the prevention of HIV-1 transmission.</p>