INTERACTIONS BETWEEN HIV-1 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 i n vitro and in vivo. Since it shares sequence similarity with the cata lytic subunit of the vacuolar ATPase (V-ATPase) and complements the lo ss of this VMA13 gene in yeast, NBP1 is the human homolog of Vma13p. D irect interactions between Nef and NBP1 were correlated with the abili ty of Nef to internalize CD4. The expression of the antisense NBP1 abr ogated these effects. We conclude that NBP1 helps to connect Nef with the endocytic pathway.