Abstract
Bacterial vaginosis (BV), a condition in which the vaginal microbiota consists of community of obligate and facultative anaerobes rather than dominated by a single species of Lactobacillus, affects ~30% of women in the US. Women with BV are at 60% increased risk for HIV acquisition and are 3-times more likely to transmit HIV to an uninfected partner. As cervicovaginal mucus (CVM) is the first line of defense against mucosal pathogens and the home of the resident vaginal microbiota, we hypothesized the barrier function of CVM to HIV may be diminished in BV. Here, we characterized CVM properties including pH, lactic acid content, and Nugent score to correlate with the microbiota community composition, which was confirmed by 16S rDNA sequencing on a subset of samples. We then quantified the mobility of fluorescently-labeled HIV virions and nanoparticles to characterize the structural and adhesive barrier properties of CVM. Our analyses included women with Nugent scores categorized as intermediate (4–6) and BV (7–10), women that were either symptomatic or asymptomatic, and a small group of women before and after antibiotic treatment for symptomatic BV. Overall, we found that HIV virions had significantly increased mobility in CVM from women with BV compared to CVM from women with Lactobacillus crispatus-dominant microbiota, regardless of whether symptoms were present. We confirmed using nanoparticles and scanning electron microscopy that the impaired barrier function was due to reduced adhesive barrier properties without an obvious degradation of the physical CVM pore structure. We further confirmed a similar increase in HIV mobility in CVM from women with Lactobacillus iners-dominant microbiota, the species most associated with transitions to BV and that persists after antibiotic treatment for BV. Our findings advance the understanding of the protective role of mucus and highlight the interplay between vaginal microbiota and the innate barrier function mucus.
Highlights
Bacterial vaginosis (BV) is a highly prevalent vaginal condition that affects approximately 30% of women in the US and as many as 44% of women in sub-Saharan Africa [1,2,3]
We found that mucus from women with BV and women with Lactobacillus iners were permissive to human immunodeficiency virus (HIV)-1, which may allow the virus to more reach target cells
These findings are in agreement with the observed increased risk for HIV acquisition seen in women with BV and L. iners bacteria
Summary
Bacterial vaginosis (BV) is a highly prevalent vaginal condition that affects approximately 30% of women in the US and as many as 44% of women in sub-Saharan Africa [1,2,3]. In a recent prospective cohort of South African women, it was found that women with high bacterial diversity and low Lactobacillus abundance had a 4-fold increase in incident HIV infection compared to women with Lactobacillus crispatus-dominant vaginal microbiota [12]. In a cohort analysis of HIV-1 seropositive women, BV was associated with a 3-fold increased risk of female-to-male transmission [13]. Many hypotheses to explain the association between BV and HIV acquisition and transmission risk focus on the impact that vaginal bacteria have on tissue integrity, inflammation, elevation of pro-inflammatory cytokines/chemokines, and recruitment and activation of HIV target cells [12, 14, 15]. The first line of defense for the mucosa, and the home of the resident microbiota, is the mucus coating the cervicovaginal epithelium. Cervicovaginal mucus (CVM) both lubricates and protects the underlying epithelium, serving as the first line of defense against viral acquisition and
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