PHYSICAL INTERACTION OF THE HIV-1 NEF PROTEIN WITH BETA-COP, A COMPONENT OF NON-CLATHRIN-COATED VESICLES ESSENTIAL FOR MEMBRANE TRAFFIC

Nef is a 27-kDa myristylated protein conserved in most human immunodef iciency virus (HIV)-1, HIV-2, and simian immunodeficiency virus isolat es. Simian immunodeficiency virus Nef is required in macaques for both high viral load and full pathological effects. Nef down-regulates the cell surface expression of CD4 by a posttranslational mechanism that is not yet fully elucidated. We have used the yeast two-hybrid system to identify cellular proteins that interact with Nef. A cDNA was isola ted which encodes a COOH-terminal fragment of human beta-COP, a major coat component of non-clathrin-coated vesicles. Nef and beta-COP inter acted in vitro and were found to be physically associated in HIV-1-inf ected cells by co immunoprecipitation. These observations suggest that beta-COP might be one of the cellular mediators of Nef function in HI V-1-infected cells.