HIV-1 induces DCIR expression in CD4+ T cells

• Published in: PLoS pathogens Vol. 6; no. 11; p. e1001188
• Main Authors: Lambert, Alexandra A, Imbeault, Michaël, Gilbert, Caroline, Tremblay, Michel J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.11.2010; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Antigen-Presenting Cells; Apoptosis; Apoptosis-inducing factor; Blotting, Western; Case-Control Studies; Catalase - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cells, Cultured; Chronic infection; Dendritic cells; Dendritic Cells - metabolism; Dendritic Cells - virology; Flow Cytometry; Free radicals; HIV; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - pathogenicity; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Infection; Infectious Diseases/HIV Infection and AIDS; Inflammation; Lectins; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Lymphocytes T; Medical research; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane proteins; Microbiology/Cellular Microbiology and Pathogenesis; Mitochondria; Pathogens; Proteins; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Replication; Rheumatoid arthritis; Studies; Viremia - genetics; Viremia - metabolism; Viremia - virology; Virology/Immunodeficiency Viruses; Virus Internalization; Virus Replication
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1001188

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.