Negative Factor Protein Nef (Nef)

Nef (Negative factor) is an accessory protein encoded by HIV-1, HIV-2, and simian immunodeficiency virus (SIV). It is a 27-kDa myristoylated protein abundantly produced during the early phase of the viral replication cycle. Nef lacks intrinsic enzymatic activity but acts as a multivalent adaptor protein, interacting with various host cell proteins to modulate cellular processes. Its main functions include immune evasion, enhancement of viral infectivity and replication, and modulation of host signaling. Nef achieves immune evasion by downregulating cell surface molecules such as CD4 and MHC-I, and modulates intracellular trafficking pathways. It is a promising target for antiretroviral drug discovery.

Nef modulates host cell functions through protein-protein interactions, altering intracellular trafficking pathways and downregulating key surface molecules. It also lowers the activation threshold for T-cell receptor signaling.