Vaginal Microbiota and Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus

A collaborator, Dr. Sam Lai, has been studying cervicovaginal mucus (CVM) properties for quite some time. He did his Postdoctoral fellowship with Dr. Richard Cone at Johns Hopkins University, who is well-known is the field having written some of the main reviews on the topic. We worked with him to established a correlation between the composition of the vaginal microbiota and entrapment of HIV-1 particles by CVM. The work was recently published in the journal mBio and shows that communities dominated by Lactobacillus crispatus (CST I) are better changing the properties of CVM to trap HIV-1 particles than other communities. CVM associated with vaginal communities dominated by Lactobacillus iners do not have these properties. These two Lactobacillus spp. are quite different genomically, but also produce very different ratio of D/L lactic acid, with L. crispatus producing both isomers, but more D(-), while L. iners producing almost exclusively the L(+) isomers. This ratio could contribute to CVM protective properties. However, other factors are certainly playing a role. 

Here is the abstract of the paper, which you can find here: Nunn KL, Wang Y-Y, Harit D, Humphrys MS, Ma B, Cone R, Ravel J, Lai SK. 2015 Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. mBio 6:e01084-15.

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.