Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV-1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV-1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis-exposed LCs efficiently transmitted HIV-1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV-1 variants that establish infection after sexual transmission, the so-called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV-1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV-1 infection.

中文翻译：

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阴道细菌 Prevotella timonensis 将保护性朗格汉斯细胞转化为 HIV-1 病毒传播库

阴道微生物群的失调与 HIV-1 的获得增加有关，但潜在的细胞机制仍不清楚。阴道朗格汉斯细胞 (LCs) 通过自噬介导的 HIV-1 降解来防止黏膜 HIV-1 感染。由于 LC 与阴道微生物组的细菌成员持续接触，我们研究了共生和生态失调相关的阴道（一种）需氧细菌种类对 LC 抗病毒功能的影响。大多数测试的细菌不影响 LC 的 HIV-1 限制功能。然而，Prevotella timonensis诱导阴道 LC 大量摄取 HIV-1。内化的病毒在几天内仍然具有传染性，并且吸收不受抗逆转录病毒药物的影响。P. timonensis-暴露的 LC在体外和离体都有效地将 HIV-1 传播到靶细胞。此外，P. timonensis暴露增强了 HIV-1 变体的吸收和传播，这些变体在性传播后建立感染，即所谓的传播创始人变体。因此，我们的研究结果表明，P. timonensis可能为增强阴道生态失调期间的 HIV-1 易感性奠定了基础，并提倡在细菌性阴道病期间对P. timonensis进行靶向治疗以限制 HIV-1 感染。