THE 27 KD PROTEIN ENCODED BY THE HIV NEF GENE SHARES STRUCTURAL AND FUNCTIONAL HOMOLOGIES WITH SEVERAL ONCOGENE PRODUCTS

The HIV genome contains nine coding regions, whose function in viral replication is still partially unknown. One of these, nef (Negative factor, previously called 3'-orf or orf-B), encodes a 27 kilodalton protein (p27nef) inducing an early specific immune response in infected patients. p27nef resembles an oncogene product: (a) it is myristylated on the aminoterminal glycine and is therefore associated to the cell membrane; (b) it shares homologies with pp60src, with EGF receptor and with G protein GTP binding domain; (c) it is phosphorylated on serine and threonine residues in vivo; (d) it has a GTPase activity, and (e) it is autophosphorylated on a serine residue in vitro. The role of p27nef during viral replication is still controversial; his negative role on HIV growth has been recently debated. In this paper we analyse the primary structure of p27nef and its functional properties. Strong homologies with the proteins encoded by src, erb-B-1 and ras oncogenes suggest its possible interference with the transmembrane transduction of extracellular signalling.