title: HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread.
abstract: DC-SIGN, a dendritic cell (DC)-specific lectin, mediates clustering of DCs with T lymphocytes, a crucial event in the initiation of immune responses. DC-SIGN also binds HIV envelope glycoproteins, allowing efficient virus capture by DCs. We show here that DC-SIGN surface levels are upregulated in HIV-1-infected DCs. This process is caused by the viral protein Nef, which acts by inhibiting DC-SIGN endocytosis. Upregulation of DC-SIGN at the cell surface dramatically increases clustering of DCs with T lymphocytes and HIV-1 transmission. These results provide new insights into how HIV-1 spreads from DCs to T lymphocytes and manipulates immune responses. They help explain how Nef may act as a virulence factor in vivo.
authors.affiliation: Unité Rétrovirus et Transfert Génétique, URA CNRS 1930, Institut Pasteur, 28 rue du Docteur Roux, 75724 Cedex 15, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sol-Foulon
authors.forename: Arnaud
authors.initials: A
authors.lastname: Moris
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nobile
authors.forename: Claire
authors.initials: C
authors.lastname: Boccaccio
authors.forename: Anneke
authors.initials: A
authors.lastname: Engering
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Heard
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D001692:Biological Transport; D015815:Cell Adhesion Molecules; D003713:Dendritic Cells / Q000502:physiology / Q000821:virology*; D004705:Endocytosis; D015693:Gene Products, nef / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D037181:Lectins, C-Type; D008214:Lymphocytes / Q000502:physiology / Q000821:virology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015854:Up-Regulation; D054311:nef Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D015693:Gene Products, nef; D037102:Lectins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D054311:nef Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin