The cervicovaginal mucus barrier to HIV-1 is diminished in bacterial vaginosis


Autoři: Thuy Hoang aff001;  Emily Toler aff001;  Kevin DeLong aff001;  Nomfuneko A. Mafunda aff004;  Seth M. Bloom aff004;  Hannah C. Zierden aff001;  Thomas R. Moench aff008;  Jenell S. Coleman aff009;  Justin Hanes aff001;  Douglas S. Kwon aff004;  Samuel K. Lai aff011;  Richard A. Cone aff008;  Laura M. Ensign aff001
Působiště autorů: The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff001;  Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff002;  Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff003;  Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, Massachusetts, United States of America aff004;  Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America aff005;  Harvard Medical School, Boston, Massachusetts, United States of America aff006;  Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America aff007;  Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, United States of America aff008;  Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff009;  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, United States of America aff010;  Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, UNC/NCSU Joint Department of Biomedical Engineering, Department of Microbiology & Immunology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, aff011
Vyšlo v časopise: The cervicovaginal mucus barrier to HIV-1 is diminished in bacterial vaginosis. PLoS Pathog 16(1): e1008236. doi:10.1371/journal.ppat.1008236
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008236

Souhrn

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.

Klíčová slova:

Bacterial vaginosis – HIV – HIV clinical manifestations – Lactic acid – Lactobacillus – Microbiome – Mucus – Virions


Zdroje

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