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

Autor: Hoang T; The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America., Toler E; The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America., DeLong K; The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America., Mafunda NA; Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, Massachusetts, United States of America., Bloom SM; Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, Massachusetts, United States of America.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.; Harvard Medical School, Boston, Massachusetts, United States of America., Zierden HC; The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America., Moench TR; Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, United States of America., Coleman JS; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America., Hanes J; The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, United States of America., Kwon DS; Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, Massachusetts, United States of America.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.; Harvard Medical School, Boston, Massachusetts, United States of America., Lai SK; 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, United States of America., Cone RA; Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, United States of America., Ensign LM; The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Jan 23; Vol. 16 (1), pp. e1008236. Date of Electronic Publication: 2020 Jan 23 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008236
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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