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

Nina Hertoghs,Bernadien M Nijmeijer,Persephone Borrow,Nienke H Van Teijlingen,Neeltje A Kootstra,Beatrice H Hahn,Carla M S Ribeiro,Tanja M Kaptein,John L Van Hamme,John C Kappes,Teunis B H Geijtenbeek,Angharad E Fenton-May,Philippe Gallay

doi:10.1371/journal.pone.0226651

Abstract

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.

Highlights

At the time of sexual transmission, different HIV-1 variants are present in seminal fluid and vaginal secretions, but typically only a single viral genotype establishes a new infection
Langerhans cells but not dendritic cells are more susceptible to Transmitted Founder (T/F) viruses
In order to assess whether T/F viruses are capable of infecting Langerhans cells (LCs), we first infected human skin derived activated LCs, as these have a reduced capacity to restrict HIV-1 infection, most likely due to the downregulation of langerin [4]

Summary

Introduction

At the time of sexual transmission, different HIV-1 variants are present in seminal fluid and vaginal secretions, but typically only a single viral genotype establishes a new infection. These so-called Transmitted Founder (T/F) viruses are thought to have specific properties that allow them to become transmitted to the host. Study of these phenotypes helps to provide a thorough. Funding from the US NIH, NIAID, Division of AIDS (R01 AI 114266 and R01 AI 111789), received by PB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Objectives

Methods

Results

Conclusion