アクティブボード・２０１２年　５月
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研究発表を行った学会；
・Keystone Symposia
　２０１２年　３月２６日〜３１日（Whistler, British
Columbia, Canada）

タイトル；A Small Molecule Compound that Reduces HIV-1 Nef-mediated Viral Infectivity Enhancement.

発表者；Nopporn Chutiwitoonchai　氏
　　　（熊本大学　エイズ学研究センター　鈴プロジェクト）
Abstract；
Nef, a multifunctional HIV-1 accessory protein accelerates AIDS progression, and enhances the infectivity of progeny viruses through a mechanism that is not yet understood. Our study identified the small chemical compound 2c that reduces Nef-mediated viral infectivity enhancement. 2c did not affect the efficiency of viral production itself when added to viral producer cells. However, the infectivity of the viruses produced in the presence of 2c was significantly lower than that of control viruses. Importantly, the inhibitory effect was observed with Nef+ wild-type viruses, but not with Nef-defective viruses or the Nef proline-rich PxxP motif-disrupted viruses, both of which displayed significantly reduced intrinsic infectivity. Meanwhile, the viral infectivity is also reduced by the overexpression of the SH3 domain of tyrosine kinase Hck, which binds to the PxxP motif in Nef. Importantly, 2c inhibited Hck SH3-Nef binding, which was more significant when Nef was pre-incubated with 2c prior to co-incubation with Hck, indicating that both Hck SH3 and 2c directly bind to Nef and that their binding sites overlap. These results indicate that both 2c and the Hck SH3 domain inhibit the interaction of Nef with an unidentified host protein and thereby reduce Nef-mediated infectivity enhancement. The Nef inhibitor 2c is therefore a valuable chemical probe for revealing the underlying molecular mechanism by which Nef enhances the infectivity of HIV-1.