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Plos Pathogens : Hiv-1 Induces Dcir Expression in Cd4+ T Cells, Volume 6

By Imbeault, Michae¨ L

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Book Id: WPLBN0003956673
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Pathogens : Hiv-1 Induces Dcir Expression in Cd4+ T Cells, Volume 6  
Author: Imbeault, Michae¨ L
Volume: Volume 6
Language: English
Subject: Journels, Science, Pathogens
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Pathogens
Historic
Publication Date:
Publisher: Plos

Description
Description : The C-type lectin receptor DCIR, which has been shown very recently to act as an attachment factor for HIV-1 in dendritic cells, is expressed predominantly on antigen-presenting cells. However, this concept was recently challenged by the discovery that DCIR can also be detected in CD4+ T cells found in the synovial tissue from rheumatoid arthritis (RA) patients. Given that RA and HIV-1 infections share common features such as a chronic inflammatory condition and polyclonal immune hyperactivation status, we hypothesized that HIV-1 could promote DCIR expression in CD4+ T cells. We report here that HIV-1 drives DCIR expression in human primary CD4+ T cells isolated from patients (from both aviremic/treated and viremic/treatment naive persons) and cells acutely infected in vitro (seen in both virus-infected and uninfected cells). Soluble factors produced by virusinfected cells are responsible for the noticed DCIR up-regulation on uninfected cells. Infection studies with Vpr- or Nef-deleted viruses revealed that these two viral genes are not contributing to the mechanism of DCIR induction that is seen following acute infection of CD4+ T cells with HIV-1. Moreover, we report that DCIR is linked to caspase-dependent (induced by a mitochondria-mediated generation of free radicals) and -independent intrinsic apoptotic pathways (involving the death effector AIF). Finally, we demonstrate that the higher surface expression of DCIR in CD4+ T cells is accompanied by an enhancement of virus attachment/entry, replication and transfer. This study shows for the first time that HIV-1 induces DCIR membrane expression in CD4+ T cells, a process that might promote virus dissemination throughout the infected organism.

 

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