Human immunodeficiency virus type 1 Nef protein (Nef) (Nef)

The Human immunodeficiency virus type 1 (HIV-1) Nef protein is a critical accessory factor required for efficient viral replication and the development of AIDS (UniProt P03406). Although it lacks intrinsic enzymatic activity, Nef acts as a potent molecular adaptor that hijacks host cellular machinery to promote viral survival and immune evasion (PMID: 22403440). One of its primary roles is the downregulation of cell surface molecules, most notably CD4 and Major Histocompatibility Complex class I (MHC-I), which prevents superinfection and allows infected cells to escape recognition by cytotoxic T lymphocytes (PMID: 25607362). Nef also modulates T-cell signaling pathways by interacting with host kinases like Hck and PAK2, thereby creating an environment conducive to viral production (PMID: 30305461). Because individuals infected with Nef-deficient HIV-1 strains often show delayed disease progression, Nef is considered a high-value therapeutic target. Current drug discovery efforts focus on small molecules that disrupt Nef's protein-protein interactions, although no such inhibitors have yet reached clinical approval (PMID: 30305461).

Other names

Negative factor3' ORF proteinF-proteinp27

Disruption of protein-protein interactions between Nef and host cell factors such as Src family kinases (e.g., Hck) and clathrin adaptors (e.g., AP-1, AP-2) to inhibit viral replication and restore cell-surface expression of MHC-I and CD4 (PMID: 30305461).