title: DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway.
abstract: Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor expressed at high levels on dendritic cells (DCs). This surface molecule acts as an attachment factor for HIV-1 on DCs and contributes to trans- and cis-infection pathways. Moreover, DICR is induced by HIV-1 in CD4(+) T cells and promotes virus replication in this cell type. Nothing is known hitherto about the DCIR-dependent signaling, which is induced following HIV-1 ligation. First, specific pharmacologic inhibitors were tested on HIV-1 binding/entry and, second, specific antisense oligonucleotides targeted, more specifically kinases and phosphatases, were used. Our results show that SHP-1, SHP-2, Syk, and Src kinases (ie, Src, Fyn, and Hck) as well as PKC-α and MAP kinases (ie, Erk1/2 and p38) are all involved in the DCIR-mediated signal transduction pathway triggered by HIV-1. By mutagenesis and through the use of intracellular phosphorylated peptides, we show as well a pivotal role for the tyrosine and threonine residues of the DCIR immunoreceptor tyrosine-based inhibitory motif (ITIM). Our data suggest for the first time an involvement of ITIM domain in HIV-1-mediated signaling events and a relationship between phosphorylation events and DCIR function with respect to HIV-1 biology.
authors.affiliation: Centre Hospitalier Universitaire de Québec-CHUL, 2705 Boulevard Laurier, Québec (QC), Canada.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Lambert
authors.forename: Frédéric
authors.initials: F
authors.lastname: Barabé
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D020816:Amino Acid Motifs; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D018450:Disease Progression; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000254:growth & development / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation
chemical_list: C423004:CLEC4A protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D047428:Protein Kinase Inhibitors; D011971:Receptors, Immunologic; D014443:Tyrosine; D011494:Protein Kinases