The HIV-1 Nef protein is a 27-kDa myristoylated protein that is abundantly produced during the early phase of viral replication cycle. It is highly conserved in all primate lentiviruses, suggesting that its function is essential for survival of these pathogens. The protein name "Nef" was derived from early reports of its negative effect on viral replication, thus 'negative factor' or Nef. Subsequently it has been demonstrated that Nef plays an important role in several steps of HIV replication. In addition, it appears to be a critical pathogenic factor, as Nef-deficient SIV and HIV are significantly less pathogenic than the wild-type viruses, whereas Nef-transgenic mice show many features characteristic to HIV disease.
The role of Nef in HIV-1 replication and disease pathogenesis is determined by at least four independent activities of this protein. Nef affects the cell surface expression of several cellular proteins, interferes with cellular signal transduction pathways, enhances virion infectivity and viral replication, and regulates cholesterol trafficking in HIV-infected cells.