HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread.
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.
Sol-Foulon
Nathalie
N
Unité Rétrovirus et Transfert Génétique, URA CNRS 1930, Institut Pasteur, 28 rue du Docteur Roux, 75724 Cedex 15, Paris, France.
Moris
Arnaud
A
Nobile
Cinzia
C
Boccaccio
Claire
C
Engering
Anneke
A
Abastado
Jean-Pierre
JP
Heard
Jean-Michel
JM
van Kooyk
Yvette
Y
Schwartz
Olivier
O
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
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