Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. One of the earliest and most abundantly expressed viral proteins (By similarity). In infected CD4(+) T-lymphocytes, down-regulates cell surface expression of CD4, CD28, CD3, and MHC-I or MHC-II molecules. Interferes with TCR signaling from the cell membrane. Interacts with CD247/TCRZ (TCR zeta chain) and exert potent down-regulation of cell surface TCR/CD3 complexes (By similarity). Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike (By similarity). Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. Homodimer. Interacts with host CD247/TCRZ; this interaction induces down-regulation of cell surface TCR/CD3 complexes. Associates with the inner plasma membrane through its N-terminal domain. The N-terminal domain is composed of the N-myristoyl glycine and of a cluster of positively charged amino acids. It is required for inner plasma membrane targeting of Nef and virion incorporation, and thereby for infectivity (By similarity). This isolate is from a Gambian case of 'neuro-AIDS'. Belongs to the lentivirus primate group Nef protein family.