Lactic acid produced by optimal vaginal Lactobacillus spp. potently and specifically inactivates HIV-1 in vitro by targeting the viral RNA genome and reverse transcriptase Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1371/journal.ppat.1013594
· OA: W4415048349
Vaginal microbiota modulates susceptibility to sexually transmitted infections and produces carboxylic acid metabolites that have antimicrobial activity; however, their activity against viral sexually transmitted infections is not well defined. We determined the HIV-1 virucidal activity of lactic acid (LA), short chain fatty acids (SCFAs), and succinic acid, representing conditions observed in women with an optimal Lactobacillus -dominated vaginal microbiota compared to women with bacterial vaginosis. Virucidal activity against enveloped HIV-1 and HSV-2, the non-enveloped HPV16, and the mechanism by which LA inactivates HIV-1 was further assessed. LA was > 10-fold more potent at inactivating an HIV-1 transmitted/founder strain than SCFAs and succinic acid when tested at an equivalent 20 mM of protonated acid (p≤0.05). While LA decreased HIV-1 infectivity by >10 3 -fold, virions were intact, expressed a similar gp120:p24 ratio, and showed only a 2-fold decrease in CD4 binding compared to untreated HIV-1 (p≤0.05). Treatment of recombinant gp120 with LA revealed no major conformational changes by small angle X-ray scattering. LA treatment of HIV-1 resulted in an 80% decrease in virion-associated reverse transcriptase activity compared to untreated virus (p < 0.01), which was more potent than acetic acid or HCl-adjusted media at the same pH, with this effect observed in the presence of cervicovaginal fluid. LA decreased HIV-1 virion-associated RNA levels by ∼50% compared to untreated virus (p < 0.001), acetic acid or HCl acidified media. In contrast, HSV-2 virucidal activity of LA was similar to acetic acid and HCl-acidified media while HPV16 was acid-resistant. Our results demonstrate LA’s potent and specific HIV-1 virucidal activity compared to SCFAs and succinic acid found in the female reproductive tract, and its HIV-1 virucidal mechanism mediated by penetration of the viral membrane and core to target a key viral enzyme and nucleic acid. These findings have implications for the vaginal transmission of HIV to partners and neonates during birth.
