Sexually transmitted founder HIV-1 viruses are relatively resistant to Langerhans cell-mediated restriction

Autoři: Nina Hertoghs aff001;  Bernadien M. Nijmeijer aff001;  Nienke H. van Teijlingen aff001;  Angharad E. Fenton-May aff002;  Tanja M. Kaptein aff001;  John L. van Hamme aff001;  John C. Kappes aff003;  Neeltje A. Kootstra aff001;  Beatrice H. Hahn aff004;  Persephone Borrow aff002;  Carla M. S. Ribeiro aff001;  Teunis B. H. Geijtenbeek aff001
Působiště autorů: Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands aff001;  Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom aff002;  Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America aff003;  Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


A single HIV-1 variant establishes infection of the host after sexual contact. Identifying the phenotypic characteristics of these Transmitted Founder (T/F) viruses is important to understand the restriction mechanisms during transmission. Langerhans cells (LCs) are the mucosal dendritic cell subset that has been shown to have a protective role in HIV-1 transmission. Immature LCs efficiently capture and degrade HIV-1 via langerin-mediated restriction. Here we have investigated the capacity of T/F HIV-1 strains to infect mucosal Langerhans cells (LCs). Notably, most T/F variants efficiently infected immature LCs derived from skin and vaginal tissue in contrast to chronic HIV-1 laboratory strains. Next we screened a panel of T/F viruses and their matched 6-month consensus sequence viruses. Interestingly most T/F variants infected immature LCs whereas donor-matched 6-month consensus sequence viruses had lost the ability to infect LCs. However, we also identified 6-month consensus sequence viruses that had retained an ability to infect LCs similar to that of the donor-matched T/F virus. Moreover, some T/F viruses and 6-month consensus sequence viruses were unable to infect immature LCs. Further analyses indicated that T/F viruses are less sensitive to langerin-mediated restriction. These data suggest that T/F HIV-1 variants have the ability to infect immature LCs, which will facilitate transmission.

Klíčová slova:

Dendritic cells – Flow cytometry – HIV-1 – Langerhans cells – Sexually transmitted diseases – Skin infections – Skin tissue – Viral transmission and infection


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2019 Číslo 12
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