HIV-1 Induces DCIR Expression in CD4+ T Cells

PLoS Pathogens

Caroline Gilbert¹  Alexandra A. Lambert¹  Michaël Imbeault¹  Michel J. Tremblay² 

[1] Centre Hospitalier Universitaire de Québec-CHUL, Québec, Canada;Département de Microbiologie-Infectiologie et Immunologie, Université Laval, Québec, Canada

关键词: T cells;    Apoptosis;    HIV-1;    Flow cytometry;    Viral replication;    Cell staining;    Mitochondria;    Free radicals;   

DOI  :  10.1371/journal.ppat.1001188

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 virus-infected 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.

【 授权许可】

CC BY