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HIV-1 induces DCIR expression in CD4+ T cells.

Published version
Peer-reviewed

Type

Article

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Authors

Lambert, Alexandra A 
Imbeault, Michaël 
Gilbert, Caroline 
Tremblay, Michel J 

Abstract

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.

Description

Keywords

Antigen-Presenting Cells, Apoptosis, Blotting, Western, CD4-Positive T-Lymphocytes, Case-Control Studies, Catalase, Cells, Cultured, Dendritic Cells, Flow Cytometry, HIV Infections, HIV-1, Humans, Lectins, C-Type, Membrane Glycoproteins, Receptors, Immunologic, Viremia, Virus Internalization, Virus Replication

Journal Title

PLoS Pathog

Conference Name

Journal ISSN

1553-7366
1553-7374

Volume Title

6

Publisher

Public Library of Science (PLoS)