Interactions between HIV1 Nef and vacuolar ATPase facilitate the internalization of CD4.
CD4 is the primary receptor for the human immunodeficiency virus (HIV). Nef is an accessory protein of HIV that decreases the expression of CD4 on the surface of infected cells. In this study, we identified the Nef binding protein 1 (NBP1), which interacts specifically with Nef in vitro and in vivo. Since it shares sequence similarity with the catalytic subunit of the vacuolar ATPase (V-ATPase) and complements the loss of this VMA13 gene in yeast, NBP1 is the human homolog of Vma13p. Direct interactions between Nef and NBP1 were correlated with the ability of Nef to internalize CD4. The expression of the antisense NBP1 abrogated these effects. We conclude that NBP1 helps to connect Nef with the endocytic pathway.
Lu
X
X
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, 94143-0703, USA.
Yu
H
H
Liu
S H
SH
Brodsky
F M
FM
Peterlin
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D019556:COS Cells; D002384:Catalysis; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D015693:Gene Products, nef / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D002966:Clathrin; D015693:Gene Products, nef; C110852:Nef receptor; D016376:Oligonucleotides, Antisense; D015728:Receptors, HIV; D054311:nef Gene Products, Human Immunodeficiency Virus; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases