title: Hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2) are involved in the down-regulation of CD1a lipid antigen presentation by HIV-1 Nef in dendritic cells.
abstract: Dendritic cells (DCs) play a major role in in vivo pathogenesis of HIV-1 infection. Therefore, DCs may provide a promising strategy to control and eventually overcome the fatal infection. Especially, immature DCs express all CD1s, the non-MHC lipid antigen -presenting molecules, and HIV-1 Nef down-regulates CD1 expression besides MHC. Moreover, CD1d-restricted CD4(+) NKT cells are infected by HIV-1, reducing the number of these cells in HIV-1-infected individuals. To understand the exact role of DCs and CD1-mediated immune response during HIV-1 infection, Nef down-regulation of CD1a-restricted lipid/glycolipid Ag presentation in iDCs was analyzed. We demonstrated the involvement of the association of Nef with hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2), and that Hck, which is expressed strongly in iDCs, augmented this mutual interaction. Hck might be another therapeutic target to preserve the function of HIV-1 infected DCs, which are potential reservoirs of HIV-1 even after antiretroviral therapy.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinya
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Owaki
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
authors.forename: Samantha
authors.initials: S
authors.lastname: Paoletti
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; C515907:PAK2 protein, human; D054462:p21-Activated Kinases
keywords: CD1a; Dendritic cells; HIV-1 Nef; Hemopoietic cell kinase; Lipid antigens; P-21 activated kinase 2; Sulfatide