Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota

ABSTRACT 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 th...

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Autores principales:	Kenetta L. Nunn, Ying-Ying Wang, Dimple Harit, Michael S. Humphrys, Bing Ma, Richard Cone, Jacques Ravel, Samuel K. Lai
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f06f90e916ed4739aa583d2db6aa6288
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spelling	oai:doaj.org-article:f06f90e916ed4739aa583d2db6aa62882021-11-15T15:41:31ZEnhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota10.1128/mBio.01084-152150-7511https://doaj.org/article/f06f90e916ed4739aa583d2db6aa62882015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01084-15https://doaj.org/toc/2150-7511ABSTRACT 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.Kenetta L. NunnYing-Ying WangDimple HaritMichael S. HumphrysBing MaRichard ConeJacques RavelSamuel K. LaiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kenetta L. Nunn Ying-Ying Wang Dimple Harit Michael S. Humphrys Bing Ma Richard Cone Jacques Ravel Samuel K. Lai Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota
description	ABSTRACT 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.
format	article
author	Kenetta L. Nunn Ying-Ying Wang Dimple Harit Michael S. Humphrys Bing Ma Richard Cone Jacques Ravel Samuel K. Lai
author_facet	Kenetta L. Nunn Ying-Ying Wang Dimple Harit Michael S. Humphrys Bing Ma Richard Cone Jacques Ravel Samuel K. Lai
author_sort	Kenetta L. Nunn
title	Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota
title_short	Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota
title_full	Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota
title_fullStr	Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota
title_full_unstemmed	Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota
title_sort	enhanced trapping of hiv-1 by human cervicovaginal mucus is associated with <named-content content-type="genus-species">lactobacillus crispatus</named-content>-dominant microbiota
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/f06f90e916ed4739aa583d2db6aa6288
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Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with <named-content content-type="genus-species">Lactobacillus crispatus</named-content>-Dominant Microbiota

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