Membrane microdomain interactions of the HIV-1 pathogenicity factor Nef

Principal investigator: Fackler

HIV-1 Nef manipulates host cell transport and signal transduction processes to augment virus replication in infected individuals. In funding period 1 we found that Nef (i) potently blocks a membrane microdomain associated anterograde transport pathway for plasma membrane (PM) delivery of the Src kinase Lck and other palmitoylated cargo and (ii) affects the subcellular localization of cellular enzymes with putative palmitoylation or depalmitoylation activity. The next goal will be to define the specific protein and lipid machinery involved to delineate how specificity of this uncharacterized transport pathway is achieved and how Nef disrupts these processes. These studies will yield important insight into the £mechanisms of Nef action and the anterograde transport pathways of Src kinases to the PM.