中文摘要：

锌指结构抗病毒蛋白（ZAP）能够特异性地识别病毒RNA并促进其特异性降解,从而抑制病毒的复制.ZAP不能独立地发挥抗病毒的功能,需要招募细胞内很多因子,包括外切酶复合体（exosome）、RNA解旋酶p72等.通过蛋白质组学分析方法,我们找到了与ZAP可能存在相互作用的一些蛋白质并证实蛋白磷酸酶2调节亚基A的α亚型（PR65A）与ZAP之间存在着直接的相互作用.细胞内PR65A的表达水平,降低削弱ZAP的活性,表明PR65A是ZAP发挥最佳抗病毒活性所必需的.这丰富了我们对ZAP抗病毒作用机理的认识,同时也为更好地利用其抗病毒活性提供了重要的指导.

英文摘要：

The zinc-finger antiviral protein（ZAP） is a host factor that inhibits the replication of certain viruses,including murine leukemia virus and Sindbis virus by destabilizing viral mRNA in the cytoplasm.ZAP binds to specific viral mRNAs and recruits cellular RNA degradation machinery to degrade the RNA.Identifying ZAP-interacting proteins provides a viable strategy to uncover the mechanism by which ZAP inhibits viral replication.In the present study,we developed a method to search for proteins interacting with ZAP.Lysates of ZAP-expressing cells were subjected to glycerol gradient centrifugation.Fractions co-migrating with ZAP were collected,followed by immunoprecipitation of ZAP.Proteins co-immunoprecipitated with ZAP were identified by mass spectrometric analysis.By this method,PR65A,a structural subunit of PP2A,was identified as a putative ZAP-interacting protein.Coimmunoprecipitation assays confirmed the interaction between PR65A and ZAP in an RNA-independent manner.Downregulation of PR65A reduced the antiviral activity of ZAP.We conclude that PR65A interacts with ZAP and is required for the optimal antiviral activity of ZAP.