Interactions of HIV-1 Nef with cellular signal transducing proteins

Nef is a 27-34 kD myristoylated protein unique to primate lentiviruses. A f unctional Nef gene is important for development of high viremia and simian AIDS in SIV infected rhesus macaques (1). In a transgenic mouse model expre ssion of Nef protein alone when expressed under a CD4-promoter is sufficien t to cause an AIDS like disease (2). A critical role for Nef in development of AIDS in humans is suggested by the observation that some individuals wi th a long-term nonprogressive HIV-1 infection are infected with viruses car rying naturally occurring Nef deletions (3-5). The mechanism of Nef action remains incompletely understood, but multiple lines of evidence point out t o a role in modulation of cellular signaling pathways via physical and func tional interactions with host cell proteins.