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HIV Mobile in Cervicovaginal Mucus of Women With
Bacterial Vaginosis / Risk for HIV Aquisition
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HIV Research for Prevention (HIVR4P), October 17-19, 2016, Chicago
Mark Mascolini
Cervicovaginal mucus (CVM) traps HIV in women with healthy vaginal microbiota, but HIV virions pass freely through CVM from women with bacterial vaginosis [1]. Those findings from an ex vivo analysis of CVM from women with and without bacterial vaginosis add to the understanding of natural defenses against HIV in women.
Researchers from Baltimore's Johns Hopkins University who conducted this study noted that CVM "is the first line of defense against viral infection in the female reproductive tract." They have engineered a system that allows them to track noninfectious mucus-penetrating particles and HIV virions in CVM and to determine whether each is trapped by adhesion or steric properties* [2]. Virions that pass through CVM unimpeded can go on to establish infection in target cells and tissues, but virions trapped in CVM will be cleared or inactivated by normal mucus turnover.
The Hopkins team aimed to determine whether bacterial vaginosis affects HIV transport in mucus because women with vaginosis run a higher risk of acquiring or transmitting HIV [3,4]. The study used undiluted CVM freshly obtained from women with normal vaginal microbiota or with bacterial vaginosis. A multiple particle tracking system employs a fluorescent microscope fitted with a high-resolution camera that records diffusion of fluorescent mucus-penetrating particles or HIV virions over time in mucus samples. Particle and virion videos yield trajectories that can be converted into time-averaged mean-square displacements, which indicate how far a particle or virion moves in a given time. Mucus-penetrating particles measure about 120 nm, similar to the approximate 110-nm size of HIV virions.
Three major findings emerged for multiple particle tracking of mucus-penetrating particles and HIV virions. First, mucus-penetrating particles moved rapidly through CVM from women with healthy Lactobacilli, but the similarly sized HIV virions got trapped. Free movement of mucus-penetrating particles indicates that HIV is not sterically trapped in CVM, so HIV must be trapped by adhesion. And adhesion depends on the chemical structure of mucin proteins.
Second, HIV moved freely in CVM from women with symptomatic bacterial vaginosis--or asymptomatic vaginosis--even after antibiotic treatment of vaginosis. HIV also proved highly mobile in CVM dominated by Lactobacillus iners** but not in CVM dominated by Lactobacillus crispatus, a bacterium that produces beneficial microbiota in the vagina and gastrointestinal tract.
Third, HIV mobility in CVM correlated positively with higher CVM pH and inversely with lactic acid content.
The Hopkins team concluded that HIV virions get trapped by adhesion in CVM from women with vaginal microbiota dominated by healthy Lactobacilli but HIV moves freely through CVM of women with bacterial vaginosis. Those findings suggest that "bacteria modify the mucin proteins in a way that compromises the barrier properties" of CVM. The investigators propose that "interactions between vaginal microbiota and CVM may have important implications for HIV transmission."
References
1. Hoang T, DeLong K, Toler E, et al. Dysbiosis in vaginal microbiota alters cervicovaginal mucus barrier properties to HIV. HIV Research for Prevention (HIVR4P 2016), October 17-19, 2016, Chicago. Abstract P14.09.
2. Ensign LM, Henning A, Schneider CS, et al. Ex vivo characterization of particle transport in mucus secretions coating freshly excised mucosal tissues. Mol Pharm. 2013;10:2176-2182.
3. Thurman AR, Doncel GF. Innate immunity and inflammatory response to Trichomonas vaginalis and bacterial vaginosis: relationship to HIV acquisition. Am J Reprod Immunol. 2011;65:89-98.
4. Mirmonsef P, Krass L, Landay A, Spear GT. The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract. Curr HIV Res. 2012;10:202-210.
*The researchers explained that mucus consists of high molecular weight mucin proteins that form a tangled net. Anything too big to fit through the pores of that net is said to be blocked sterically.
**Lactobacillus iners is typically considered a constituent of the healthy vagina but has been linked to bacterial vaginosis (both more likely to result in vaginosis relapse and more likely to be present after antibiotic treatment).
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