The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane.
The HIV Nef protein down-regulates the cell surface expression of CD4 and of MHC I at least in part through accelerated endocytosis. To investigate further the mechanism of this effect, we created chimeric integral membrane proteins comprising the extracellular and transmembrane regions of CD4 or CD8 and Nef as the cytoplasmic domain. These fusion molecules could down-modulate CD4 in trans in a dileucine-dependent manner. Furthermore, in spite of lacking receptor-derived internalization signals, the Nef-containing chimeras underwent both Golgi retention and rapid endocytosis via clathrin-coated pits. Taken together, these data suggest that Nef down-regulates CD4 and probably MHC I by physically connecting these receptors with sorting pathways in the Golgi and at the plasma membrane.
Mangasarian
A
A
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Foti
M
M
Aiken
C
C
Chin
D
D
Carpentier
J L
JL
Trono
D
D
D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D015693:Gene Products, nef / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D016827:CD8 Antigens; D015693:Gene Products, nef; D011993:Recombinant Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus