Biological properties of Nef and its pathogenic potential in HIV-1 related central nervous system dysfunction.

Although many studies on the biochemical and physiological properties of Nef have been carried out, the functional role in HIV-1-infected cells has not yet been clearly elucidated. Results obtained in GTP/ATP-binding assays did not reveal unambiguous proof of a G-protein-like activity of Nef. Also, the lack of ADP-ribosylation capacity of Nef expected for G-proteins suggests that Nef may not be directly involved in second-messenger signalling pathways via G-proteins. On the other hand it was shown that Nef is affected by phosphorylation-dephosphorylation events, pointing to a possible mechanism for regulation of Nef-mediated activities in the cell. The distribution of Nef in different cellular compartments of astrocytes also implies a variety of Nef functions, depending on its cellular localization. It is possible that extracellular Nef, due to cell lysis or active secretion, exerts a direct influence on the ion channels of brain cells leading to a physiological dysfunction of the cells without visible cytotoxic defects in HIV-1-induced brain disease