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

• Published in: PloS one Vol. 14; no. 12; p. e0226651
• Main Authors: Hertoghs, Nina, Nijmeijer, Bernadien M., van Teijlingen, Nienke H., Fenton-May, Angharad E., Kaptein, Tanja M., van Hamme, John L., Kappes, John C., Kootstra, Neeltje A., Hahn, Beatrice H., Borrow, Persephone, Ribeiro, Carla M. S., Geijtenbeek, Teunis B. H.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.12.2019; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Analysis; Antigens, CD - metabolism; Biology and Life Sciences; Blood & organ donations; Blood banks; Cells, Cultured; Clinical medicine; Cloning; Conserved sequence; Dendritic cells; Disease transmission; Health aspects; HEK293 Cells; HIV; HIV-1 - pathogenicity; Host-Pathogen Interactions; Human immunodeficiency virus; Humans; Immunoglobulins; Immunology; Infection; Infections; Laboratories; Langerhans cells; Langerhans Cells - immunology; Langerhans Cells - virology; Lectins, C-Type - metabolism; Mannose-Binding Lectins - metabolism; Medical ethics; Medicine; Medicine and Health Sciences; Mucosa; Plasmids; Raltegravir; Research and Analysis Methods; Sexually transmitted diseases; Skin; STD; Strains (organisms); Vagina; Viruses; Netherlands; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226651

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.