Journal
EMBO JOURNAL
Volume 41, Issue 19, Pages -Publisher
WILEY
DOI: 10.15252/embj.2022110629
Keywords
HIV-1; Langerhans cells (LCs); Prevotella timonensis; transmission; vaginal microbiome
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Funding
- AMC PhD Scholarship
- Dutch Research Council (NWO-ZonMw) VIDI grant [91718331]
- Dutch Research Council (NWO-ZonMW) TOP grant [91218017]
- European Research Council (ERC) [670424]
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Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition. Prevotella timonensis induces uptake and transmission of HIV-1 by vaginal Langerhans cells, enhancing infection susceptibility, thus advocating targeted treatment of P. timonensis to limit HIV-1 infection.
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.
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