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Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota
Open accessAbstract
UNLABELLED: Cervicovaginal mucus (CVM) can provide a barrier that precludes HIV and other sexually transmitted virions from reaching target cells in the vaginal epithelium, thereby preventing or reducing infections. However, the barrier properties of CVM differ from woman to woman, and the causes of these variations are not yet well understood. Using high-resolution particle tracking of fluorescent HIV-1 pseudoviruses, we found that neither pH nor Nugent scores nor total lactic acid levels correlated significantly with virus trapping in unmodified CVM from diverse donors. Surprisingly, HIV-1 was generally trapped in CVM with relatively high concentrations of d-lactic acid and a Lactobacillus crispatus-dominant microbiota. In contrast, a substantial fraction of HIV-1 virions diffused rapidly through CVM with low concentrations of d-lactic acid that had a Lactobacillus iners-dominant microbiota or significant amounts of Gardnerella vaginalis, a bacterium associated with bacterial vaginosis. Our results demonstrate that the vaginal microbiota, including specific species of Lactobacillus, can alter the diffusional barrier properties of CVM against HIV and likely other sexually transmitted viruses and that these microbiota-associated changes may account in part for the elevated risks of HIV acquisition linked to bacterial vaginosis or intermediate vaginal microbiota. IMPORTANCE: Variations in the vaginal microbiota, especially shifts away from Lactobacillus-dominant microbiota, are associated with differential risks of acquiring HIV or other sexually transmitted infections. However, emerging evidence suggests that Lactobacillus iners frequently colonizes women with recurring bacterial vaginosis, raising the possibility that L. iners may not be as protective as other Lactobacillus species. Our study was designed to improve understanding of how the cervicovaginal mucus barrier against HIV may vary between women along with the vaginal microbiota and led to the finding that the vaginal microbiota, including specific species of Lactobacillus, can directly alter the diffusional barrier properties of cervicovaginal mucus. This work advances our understanding of the complex barrier properties of mucus and highlights the differential protective ability of different species of Lactobacillus, with Lactobacillus crispatus and possibly other species playing a key role in protection against HIV and other sexually transmitted infections. These findings could lead to the development of novel strategies to protect women against HIV.
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“A Lactobacillus crispatus-dominant microbiota has been shown to impede the diffusion of HIV-1 virions, in contrast to the rapid diffusion observed with a Lactobacillus iners-dominant microbiota, or when Gardnerella vaginalis is present in significant amounts (Nunn et al., 2015).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Nunn et al., 2015
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“A L. crispatus-dominated vaginal microbiota produces high concentrations of D-lactate which has been recently shown to increase cervicovaginal mucus viscosity and enhance its viral particle trapping potential (Nunn et al., 2015), and tends to have the least likelihood of viral infections of all CSTs (Borgdorff et al., 2014).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Nunn et al., 2015
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Metadata
- Authors
- Nunn, K. L., Wang, Y.-Y., Harit, D., Humphrys, M. S., Ma, B., Cone, R., Ravel, J., & Lai, S. K.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA
- University of Maryland, Baltimore (US)
- Johns Hopkins University (US)
- Corresponding author
- Lai, Samuel K.
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2015-10-30
- Volume
- 6
- Issue
- 5
- Pages
- e01084-15
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC4611035
- OpenAlex
- W2172682788
- Cited by
- 194
- References
- 49
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 17 · 2022: 24 · 2021: 34 · 2020: 18 · 2019: 17 · 2018: 22 · 2017: 16 · 2016: 12 · 2015: 3
- FWCI
- 14.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (1f32ai102535-01)
- University of North Carolina at Chapel Hill
- National Institute of General Medical Sciences (R25GM089569)
- National Institute of Allergy and Infectious Diseases (U19AI084044, R21AI093242, F32 AI102535, U19AI096398, P30 AI50410, 1F32AI102535, P30AI050410)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- HIV-1, cervicovaginal mucus, vaginal microbiota, Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, bacterial vaginosis, mucus barrier, virus trapping, D-lactate, HIV acquisition, sexually transmitted infections, particle tracking
- MeSH terms
- Adult, Cervix Uteri, Female, Gardnerella vaginalis, Humans, Hydrogen-Ion Concentration, Lactobacillus, Mucus, Vagina, HIV-1, Lactic Acid, Young Adult
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