Protein Nef, HIV2 (Nef)

The human immunodeficiency virus (HIV) accessory protein Nef plays a major role in establishing and maintaining infection, particularly through immune evasion. Many HIV-2 infected people  experience long-term viral control and survival, similar to HIV-1 elite control. HIV-2 Nef and HIV-1 Nef have overlapping but distinct functions. In primates and humans, deletions in Nef are clearly associated with low viral load and delayed disease progression. HIV-1 and HIV-2 Nef down-regulate membrane proteins such as CD3, CD4 and CD28, up-regulate Fas proteins on infected cells, and regulate signaling pathways through interaction with kinases. However, HIV-2 Nef uses its C-terminal region, which is absent in HIV-1 Nef, to down-regulate MHC Class I molecules by binding to the AP-1 complex.