| Autor: |
van Teijlingen, Nienke H, Helgers, Leanne C, Sarrami‐Forooshani, Ramin, Zijlstra‐Willems, Esther M, van Hamme, John L, Segui‐Perez, Celia, van Smoorenburg, Marleen Y, Borgdorff, Hanneke, van de Wijgert, Janneke HHM, van Leeuwen, Elisabeth, van der Post, Joris AM, Strijbis, Karin, Ribeiro, Carla MS, Geijtenbeek, Teunis BH |
| Předmět: |
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| Zdroj: |
EMBO Journal; 10/4/2022, Vol. 41 Issue 19, p1-13, 13p |
| Abstrakt: |
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. Synopsis: Vaginal Langerhans cells (LCs) destroy HIV‐1 upon capture, thereby protecting against infection. Investigation of various commensal and dysbiotic bacteria reveals that Prevoptella timonensis selectively subverts these restrictive cells into reservoirs mediating efficient HIV‐1 transmission to target T cells.P. timonensis, but not other dysbiosis‐associated vaginal bacteria, enhances HIV‐1 uptake in LCs.P. timonensis transforms LCs into HIV‐1 reservoirs.HIV‐1 remains infectious for several days in P. timonensis‐exposed LCs.P. timonensis‐exposed LCs efficiently transmit captured HIV‐1 to target cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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