Table_1_Extracellular Vesicles Generated by Gram-Positive Bacteria Protect Human Tissues Ex Vivo From HIV-1 Infection.xlsx

Vaginal microbiota dominated by lactobacilli protects women from sexually transmitted infection, in particular HIV-1. This protection is, in part, mediated by Lactobacillus-released extracellular vesicles (EVs). Here, we investigated whether EVs derived from other Gram-positive bacteria also present in healthy vaginas, in particular Staphylococcus aureus, Gardnerella vaginalis, Enterococcus faecium, and Enterococcus faecalis, can affect vaginal HIV-1 infection. We found that EVs released by these bacteria protect human cervico-vaginal tissues ex vivo and isolated cells from HIV-1 infection by inhibiting HIV-1-cell receptor interactions. This inhibition was associated with a diminished exposure of viral Env by steric hindrance of gp120 or gp120 modification evidenced by the failure of EV-treated virions to bind to nanoparticle-coupled anti-Env antibodies. Furthermore, we found that protein components associated with EV’s outer surface are critical for EV-mediated protection from HIV-1 infection since treatment of bacteria-released EVs with proteinase K abolished their anti-HIV-1 effect. We identified numerous EV-associated proteins that may be involved in this protection. The identification of EVs with specific proteins that suppress HIV-1 may lead to the development of novel strategies for the prevention of HIV-1 transmission.

以乳杆菌为主体的阴道微生物群可抵御女性感染性传播疾病，尤其是HIV-1。这种保护作用部分是通过乳杆菌释放的细胞外囊泡（EVs）介导的。在本研究中，我们探讨了存在于健康阴道中的其他革兰氏阳性细菌（如金黄色葡萄球菌、加德纳菌、粪肠球菌和粪肠球菌）来源的EVs是否能够影响阴道HIV-1感染。我们发现，这些细菌释放的EVs可以体外保护人类宫颈阴道组织及分离的细胞免受HIV-1感染，通过抑制HIV-1与细胞受体的相互作用来实现。这种抑制作用与病毒Env暴露减少相关，这通过EV处理的病毒颗粒无法与纳米颗粒偶联的抗Env抗体结合得到证实，表明gp120或gp120的立体阻碍或修饰。此外，我们发现与EV外表面相关的蛋白质成分对于通过EV介导的保护免受HIV-1感染至关重要，因为用蛋白酶K处理细菌释放的EVs会消除其抗HIV-1效果。我们鉴定出许多可能与这种保护作用相关的EV相关蛋白质。鉴定出具有抑制HIV-1作用的特定蛋白质的EVs可能引领新型预防HIV-1传播策略的开发。