Prevotella timonensis Bacteria Associated With Vaginal Dysbiosis Enhance Human Immunodeficiency Virus Type 1 Susceptibility Of Vaginal CD4+ T Cells

Author:

van Teijlingen Nienke H123ORCID,van Smoorenburg Marleen Y12ORCID,Sarrami-Forooshani Ramin14ORCID,Zijlstra-Willems Esther M12,van Hamme John L12ORCID,Borgdorff Hanneke56ORCID,van de Wijgert Janneke H H M7ORCID,van Leeuwen Elisabeth3ORCID,van der Post Joris A M3ORCID,Strijbis Karin8ORCID,Ribeiro Carla M S12ORCID,Geijtenbeek Teunis B H12ORCID

Affiliation:

1. Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands

2. Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands

3. Department of Obstetrics and Gynecology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam , The Netherlands

4. Advanced Therapy Medicinal Product Department, Breast Cancer Research Center, Motamed Cancer Institute, Academic center for Education, Culture and Research , Tehran , Iran

5. Amsterdam Institute for Global Health and Development, 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 of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University , Utrecht , The Netherlands

Abstract

Abstract Dysbiosis of the vaginal microbiome poses a serious risk for sexual human immunodeficiency virus type 1 (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 P timonensis–enhanced infection. Our study shows that the vaginal microbiome directly affects mucosal CD4+ T-cell susceptibility, emphasizing importance of vaginal dysbiosis diagnosis and treatment.

Funder

Dutch Research Council

European Research Council

Publisher

Oxford University Press (OUP)

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