Karn T, Hock B, Holtrich U, Adamski M, Strebhardt K, Rübsamen-Waigmann H
Chemotherapeutisches Forschungsinstitut, Frankfurt, Federal Republic of Germany.
Virology. 1998 Jun 20;246(1):45-52. doi: 10.1006/viro.1998.9157.
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, Nefin 1, with characteristics of an adaptor protein and strong expression in all human hematopoietic tissues. Nefin 1 binds through an amino-terminal domain, which is related to SH3 domains. For interaction of Nef with Nefin 1, 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 pathogenicity in vivo.
人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）的Nef基因与致病性有关；然而，Nef诱发疾病的机制仍不清楚。HIV-1毒株的Nef与酪氨酸激酶（如HCK和LCK）以及丝氨酸/苏氨酸激酶的相互作用表明其对细胞信号转导有影响。我们已经证实HCK与HIV-1 B亚型Nef结合，并证明其与E亚型Nef蛋白的相互作用同样强烈，但与HIV-2 A亚型（HIV-2D194）的Nef结合较弱。然而，未观察到与HIV-2 B亚型Nef（HIV-2D205）的结合。相反，该蛋白与一种新型细胞蛋白Nefin 1结合，Nefin 1具有衔接蛋白的特征且在所有人类造血组织中均有强烈表达。Nefin 1通过与SH3结构域相关的氨基末端结构域进行结合。对于Nef与Nefin 1的相互作用，PxxP基序和分子的三维构象似乎是必需的。总之，本研究表明，HIV-1和HIV-2不同毒株的Nef蛋白可能利用信号转导途径的不同元件在体内诱发致病性。
