Vaginal Bacterium Prevotella Timonensis Turns Protective Langerhans Cells Into Hiv-1 Reservoirs for Virus Dissemination Publisher Pubmed



Van Teijlingen NH^{1, 2} ; Helgers LC^{1, 2} ; Sarramiforooshani R^{1, 3} ; Zijlstrawillems EM^{1, 2} ; Van Hamme JL^{1, 2} ; Seguiperez C⁴ ; Van Smoorenburg MY^{1, 2} ; Borgdorff H⁵ ; Van De Wijgert JHHM⁶ ; Van Leeuwen E⁷ ; Van Der Post JAM⁷ ; Strijbis K⁴ ; Ribeiro CMS^{1, 2} ; Geijtenbeek TBH^{1, 2} Show Affiliations
Source: EMBO Journal Published:2022

Abstract

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. © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.