title: HIV-1 induces DCIR expression in CD4+ T cells.
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.
authors.affiliation: Centre Hospitalier Universitaire de Québec-CHUL, Québec, Canada.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Lambert
authors.forename: Michaël
authors.initials: M
authors.lastname: Imbeault
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D000938:Antigen-Presenting Cells; D017209:Apoptosis; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D016022:Case-Control Studies; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014766:Viremia / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: C423004:CLEC4A protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D002374:Catalase