Open AccessSexually transmitted founder HIV-1 viruses are relatively resistant to Langerhans cell-mediated restriction
Author(s) -
Nina Hertoghs,
Bernadien M. Nijmeijer,
Nienke H. van Teijlingen,
Angharad E. Fenton-May,
Tanja M. Kaptein,
John L. van Hamme,
John C. Kappes,
Neeltje A. Kootstra,
Beatrice H. Hahn,
Persephone Borrow,
Carla M. S. Ribeiro,
Teunis B. H. Geijtenbeek
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0226651
Subject(s) - langerin , biology , virology , transmission (telecommunications) , langerhans cell , consensus sequence , virus , genetics , antigen , dendritic cell , base sequence , gene , electrical engineering , engineering
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.