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Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid.

ABSTRACT: Women of reproductive age with a Lactobacillus-dominated vaginal microbiota have a reduced risk of acquiring and transmitting HIV and a vaginal pH of ~4 due to the presence of ~1% (wt/vol) lactic acid. While lactic acid has potent HIV virucidal activity in vitro, whether lactic acid present in the vaginal lumen inactivates HIV has not been investigated. Here we evaluated the anti-HIV-1 activity of native, minimally diluted cervicovaginal fluid obtained from women of reproductive age (n = 20) with vaginal microbiota dominated by Lactobacillus spp. Inhibition of HIVBa-L was significantly associated with the protonated form of lactic acid in cervicovaginal fluid. The HIVBa-L inhibitory activity observed in the <3-kDa acidic filtrate was similar to that of the corresponding untreated native cervicovaginal fluid as well as that of clarified neat cervicovaginal fluid subjected to protease digestion. These ex vivo studies indicate that protonated lactic acid is a major anti-HIV-1 metabolite present in acidic cervicovaginal fluid, suggesting a potential role in reducing HIV transmission by inactivating virus introduced or shed into the cervicovaginal lumen.IMPORTANCE The Lactobacillus-dominated vaginal microbiota is associated with a reduced risk of acquiring and transmitting HIV and other sexually transmitted infections (STIs). Lactic acid is a major organic acid metabolite produced by lactobacilli that acidifies the vagina and has been reported to have inhibitory activity in vitro against bacterial, protozoan, and viral STIs, including HIV infections. However, the anti-HIV properties of lactic acid in native vaginal lumen fluids of women colonized with Lactobacillus spp. have not yet been established. Our study, using native cervicovaginal fluid from women, found that potent and irreversible anti-HIV-1 activity is significantly associated with the concentration of the protonated (acidic, uncharged) form of lactic acid. This work advances our understanding of the mechanisms by which vaginal microbiota modulate HIV susceptibility and could lead to novel strategies to prevent women from acquiring HIV or transmitting the virus during vaginal intercourse and vaginal birth.

SUBMITTER: Tyssen D

PROVIDER: S-EPMC6034077 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid.

Tyssen David D Wang Ying-Ying YY Hayward Joshua A JA Agius Paul A PA DeLong Kevin K Aldunate Muriel M Ravel Jacques J Moench Thomas R TR Cone Richard A RA Tachedjian Gilda G

mSphere 20180705 4

Women of reproductive age with a <i>Lactobacillus-</i>dominated vaginal microbiota have a reduced risk of acquiring and transmitting HIV and a vaginal pH of ~4 due to the presence of ~1% (wt/vol) lactic acid. While lactic acid has potent HIV virucidal activity <i>in vitro</i>, whether lactic acid present in the vaginal lumen inactivates HIV has not been investigated. Here we evaluated the anti-HIV-1 activity of native, minimally diluted cervicovaginal fluid obtained from women of reproductive ag ...[more]

PMID: 29976641

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Project description:Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition.The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women.Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test.Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; P<.01), but infectivity was not different between groups (P?.44). During the second and third trimesters, pregnant women experienced suppression of several cervicovaginal immune mediators that included human beta defensin-2; lactoferrin; macrophage inflammatory protein-3?; regulated on activation, normally T-cell expressed and secreted; and stromal cell-derived factor-1 (all P?.05). The antimicrobial peptide elafin was significantly correlated with HIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant group (n=16). Secretory leukocyte protease inhibitor also was correlated significantly with infectivity across all visits, but in nonpregnant women only (P?.03).Cervicovaginal secretions from both pregnant and nonpregnant women contain immune mediators that are associated with HIV infectivity in an in vitro assay; however, infectivity was not different between pregnant and nonpregnant groups. If pregnant women are at increased risk for HIV infection, it is unlikely to be mediated by alterations in the effectiveness of these protective secretions.

Dataset Information

Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid.

Publications

Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid.

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