Nef Proteins of Distinct HIV-1 or -2 Isolates Differ in Their Binding Properties for HCK: Isolation of a Novel Nef Binding Factor with Characteristics of an Adaptor Protein

Autor: Karn, Thomas, Hock, Björn, Holtrich, Uwe, Adamski, Michalina, Strebhardt, Klaus, Rübsamen-Waigmann, Helga
Zdroj: Virology; June 1998, Vol. 246 Issue: 1 p45-52, 8p
Abstrakt: The Nef gene of the human and simian immunodeficiency viruses HIV and SIV has been implicated in pathogenicity; however, the mechanism by which Nef induces disease is still unknown. An impact on signal transduction in cells has been suggested by the interaction of Nef from an HIV-1 strain and tyrosine kinases like HCK and LCK as well as serine/threonine kinases. We have confirmed the binding of HCK to HIV-1 subtype B Nef and demonstrated an equally strong interaction with a subtype E Nef protein but weaker binding to Nef of HIV-2 subtype A (HIV-2D194). No binding, however, was observed to HIV-2 subtype B Nef (HIV-2D205). Instead, this protein bound to a novel cellular protein,Nefin1,with characteristics of an adaptor protein and strong expression in all human hematopoietic tissues.Nefin1binds through an amino-terminal domain, which is related to SH3 domains. For interaction of Nef withNefin1,the PxxP motif and the three-dimensional conformation of the molecule appear necessary. In conclusion, this study demonstrates that Nef proteins of divergent strains of HIV-1 and HIV-2 may use different elements of signal transduction pathways for the induction of pathogenicityin vivo.
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