Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues

• Published in: Nature communications 2019-12, Vol.10 (1), p.5656-14, Article 5656
• Main Authors: Ñahui Palomino, Rogers A., Vanpouille, Christophe, Laghi, Luca, Parolin, Carola, Melikov, Kamran, Backlund, Peter, Vitali, Beatrice, Margolis, Leonid
• Format: Article
• Language: English
• Subjects: 13; 631/326/596/2563; 692/699/255/1901; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Bacterial Proteins - chemistry; Bacterial Proteins - pharmacology; Bacterial vesicles; Extracellular vesicles; Extracellular Vesicles - chemistry; Extracellular Vesicles - metabolism; Female; HIV; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Human tissues; Humanities and Social Sciences; Humans; Infections; Lactobacilli; Lactobacillus; Lactobacillus - chemistry; Lactobacillus - isolation & purification; Lactobacillus - metabolism; Lymphocytes; Lymphocytes T; Metabolites; Microbiota - drug effects; multidisciplinary; Proteins; Science; Science (multidisciplinary); Sexually transmitted diseases; STD; Tonsil; Vagina; Vagina - microbiology; Vesicles; Virus attachment; Virus Internalization - drug effects
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13468-9

The vaginal microbiota, dominated by Lactobacillus spp., plays a key role in preventing HIV-1 transmission. Here, we investigate whether the anti-HIV effect of lactobacilli is mediated by extracellular vesicles (EVs) released by these bacteria. Human cervico-vaginal and tonsillar tissues ex vivo, and cell lines were infected with HIV-1 and treated with EVs released by lactobacilli isolated from vaginas of healthy women. EVs released by L. crispatus BC3 and L. gasseri BC12 protect tissues ex vivo and isolated cells from HIV-1 infection. This protection is associated with a decrease of viral attachment to target cells and viral entry due to diminished exposure of Env that mediates virus-cell interactions. Inhibition of HIV-1 infection is associated with the presence in EVs of several proteins and metabolites. Our findings demonstrate that the protective effect of Lactobacillus against HIV-1 is, in part, mediated by EVs released by these symbiotic bacteria. If confirmed in vivo, this finding may lead to new strategies to prevent male-to-female sexual HIV-1 transmission. Lactobacillus associates with vaginal protection from HIV-1 infection. Here, the authors show that lactobacilli extracellular vesicles contain bacterial proteins and metabolites that inhibit HIV-1 infection in T cells and in human cervico-vaginal and tonsillar tissues ex vivo via altering viral Env proteins.