Abstract
Vaginal microbiota dominated by lactobacilli protects women from sexually transmitted infection, in particular HIV-1. This protection is, in part, mediated by Lactobacillus-released extracellular vesicles (EVs). Here, we investigated whether EVs derived from other Gram-positive bacteria also present in healthy vaginas, in particular Staphylococcus aureus, Gardnerella vaginalis, Enterococcus faecium, and Enterococcus faecalis, can affect vaginal HIV-1 infection. We found that EVs released by these bacteria protect human cervico-vaginal tissues ex vivo 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.
Highlights
Lactobacillus spp. in the vaginal niche of premenopausal women, when dominant, protect from several gynaecological infections (O’Hanlon et al, 2013; Parolin et al, 2015; Nardini et al, 2016; Gosmann et al, 2017; Siroli et al, 2017; Parolin et al, 2018)
Our results demonstrated that all bacterial strains secrete extracellular vesicles (EVs) of similar size ranging from 179.07 ± 17.22 nm (G. vaginalis) to 231.97 ± 11.24 nm (S. aureus) (Figure 1A)
Our results show that the incubation of HIV-1LAI.04 with bacterial EVs led to a significant reduction in the number of HIV-1 virions captured with PG9-magnetic iron oxide nanoparticles (MNPs) antibodies in comparison with the control (Figure 7A)
Summary
Lactobacillus spp. in the vaginal niche of premenopausal women, when dominant, protect from several gynaecological infections (O’Hanlon et al, 2013; Parolin et al, 2015; Nardini et al, 2016; Gosmann et al, 2017; Siroli et al, 2017; Parolin et al, 2018). Numerous studies have reported that vaginal lactobacilli protect from HIV-1 infection through acidification of the vaginal niche, stimulation of an anti-HIV-1 immune response, and capture of HIV-1 virions by membrane lectins (Atashili et al, 2008; Petrova et al, 2013; Gosmann et al, 2017; Ñahui Palomino et al, 2017). Another mode of lactobacilli-mediated protection against HIV-1 infection was discovered, that is the release of extracellular vesicles (EVs) (Ñahui Palomino et al, 2019)
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