Implications of Nef: Host Cell Interactions in Viral Persistence and Progression to AIDS

The HIV and SIV Nef accessory proteins are potent enhancers of viral persistence and accelerate progression to AIDS in HIV-1-infected patients and non-human primate models. Although relatively small (27-35 kD), Nef can interact with a multitude of cellular factors and induce complex changes in trafficking, signal transduction, and gene expression that together converge to promote viral replication and immune evasion. In particular, Nef recruits several immunologically relevant cellular receptors to the endocytic machinery to reduce the recognition and elimination of virally infected cells by the host immune system, while simultaneously interacting with various kinases to promote T cell activation and viral replication. This review provides an overview on selected Nef interactions with host cell proteins, and discusses their possible relevance for viral spread and pathogenicity.