Prevotella timonensis bacteria associated with vaginal dysbiosis enhance HIV-1 susceptibility of vaginal CD4+ T cells

Nienke H van Teijlingen; Marleen Y van Smoorenburg; Ramin Sarrami-Forooshani; Esther M Zijlstra-Willems; John L van Hamme; Hanneke Borgdorff; Janneke Hhm van de Wijgert; Elisabeth van Leeuwen; Joris A M van der Post; Karin Strijbis; Carla M S Ribeiro; Teunis B H Geijtenbeek

doi:10.1093/infdis/jiae166

Prevotella timonensis bacteria associated with vaginal dysbiosis enhance HIV-1 susceptibility of vaginal CD4+ T cells

J Infect Dis. 2024 Apr 4:jiae166. doi: 10.1093/infdis/jiae166. Online ahead of print.

Authors

Nienke H van Teijlingen^{1

2

3}, Marleen Y van Smoorenburg^{1

2}, Ramin Sarrami-Forooshani^{1

4}, Esther M Zijlstra-Willems^{1

2}, John L van Hamme^{1

2}, Hanneke Borgdorff^{5

6}, Janneke Hhm van de Wijgert⁷, Elisabeth van Leeuwen³, Joris A M van der Post³, Karin Strijbis⁸, Carla M S Ribeiro^{1

2}, Teunis B H Geijtenbeek^{1

2}

Affiliations

¹ Amsterdam UMC, location University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, Amsterdam, the Netherlands.
² Amsterdam institute for Immunology and Infectious Diseases, Amsterdam, the Netherlands.
³ Department of Obstetrics and Gynecology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
⁴ ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
⁵ Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands.
⁶ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
⁷ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁸ Department of Biomolecular Health Sciences, Division Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands.

PMID: 38573164
DOI: 10.1093/infdis/jiae166

Abstract

Dysbiosis of the vaginal microbiome poses a serious risk for sexual HIV-1 transmission. Prevotella spp. are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished Prevotella timonensis-enhanced infection. Hence, our study shows that the vaginal microbiome directly affects mucosal CD4+ T cell susceptibility, emphasising importance of vaginal dysbiosis diagnosis and treatment.

Keywords: Prevotella timonensis; CD4+ T cells; HIV-1 susceptibility; microbiome; vaginal dysbiosis.