HIV Negative Regulatory Factor (HIV Nef)

HIV Negative Regulatory Factor (Nef) is a small, myristoylated accessory protein (27–35 kDa) encoded by primate lentiviruses including HIV-1 and HIV-2[1][7]. Despite its name, Nef is a central facilitator of HIV pathogenesis, enhancing viral replication, promoting immune evasion, and accelerating disease progression. Nef lacks intrinsic enzymatic activity and instead exerts its effects via multiple protein-protein interactions with host cellular machinery. Major biological roles include downregulation of CD4 and MHC I molecules from the cell surface—thereby enabling infected cell escape from immune surveillance—modulation of T cell receptor signaling, alteration of endosomal trafficking, and promotion of T cell activation environments favorable for viral persistence[1][4][7]. Nef is composed of a flexible, myristoylated N-terminal membrane anchor and a structured core, which together mediate binding to host kinases and adaptor protein complexes involved in trafficking[1][6]. Loss or mutation of Nef dramatically reduces HIV virulence, and attempts to therapeutically inhibit its actions are ongoing, though no Nef-directed drugs are approved to date[1][7].

Other names

NefNegative Regulatory Factornef protein

Disruption of Nef-mediated protein-protein interactions (with host kinases, adaptor protein complexes, etc.)[1][4]