TY - JOUR
T1 - Sexually transmitted founder HIV-1 viruses are relatively resistant to Langerhans cell-mediated restriction
AU - Hertoghs, Nina
AU - Nijmeijer, Bernadien M.
AU - van Teijlingen, Nienke H.
AU - Fenton-May, Angharad E.
AU - Kaptein, Tanja M.
AU - van Hamme, John L.
AU - Kappes, John C.
AU - Kootstra, Neeltje A.
AU - Hahn, Beatrice H.
AU - Borrow, Persephone
AU - Ribeiro, Carla M. S.
AU - Geijtenbeek, Teunis B. H.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85077027901&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31856198
U2 - https://doi.org/10.1371/journal.pone.0226651
DO - https://doi.org/10.1371/journal.pone.0226651
M3 - Article
C2 - 31856198
SN - 1932-6203
VL - 14
JO - PLOS ONE
JF - PLOS ONE
IS - 12
M1 - e0226651
ER -