Alvisi Gualtiero, Rawlinson Stephen M, Ghildyal Reena, Ripalti Alessandro, Jans David A
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Biochim Biophys Acta. 2008 Jan;1784(1):213-27. doi: 10.1016/j.bbapap.2007.08.021. Epub 2007 Aug 31.
The study of viral proteins and host cell factors that interact with them has represented an invaluable contribution to understanding of the physiology as well as associated pathology of key eukaryotic cell processes such as cell cycle regulation, signal transduction and transformation. Similarly, knowledge of nucleocytoplasmic transport is based largely on pioneering studies performed on viral proteins that enabled the first sequences responsible for the facilitated transport through the nuclear pore to be identified. The study of viral proteins has also enabled the discovery of several nucleocytoplasmic regulatory mechanisms, the best characterized being through phosphorylation. Recent delineation of the mechanisms whereby phosphorylation regulates nuclear import and export of key viral gene products encoded by important human pathogens such as human cytomegalovirus dengue virus and respiratory syncytial virus has implications for the development of antiviral therapeutics. In particular, the development of specific and effective kinase inhibitors makes the idea of blocking viral infection by inhibiting the phosphorylation-dependent regulation of viral gene product nuclear transport a real possibility. Additionally, examination of a chicken anemia virus (CAV) protein able to target selectively into the nucleus of tumor but not normal cells, as specifically regulated by phosphorylation, opens the exciting possibility of cancer cell-specific nuclear targeting. The study of nucleoplasmic transport may thus enable the development not only of new antiviral approaches, but also contribute to anti-cancer strategies.
对病毒蛋白及其相互作用的宿主细胞因子的研究，为理解关键真核细胞过程（如细胞周期调控、信号转导和转化）的生理学以及相关病理学做出了宝贵贡献。同样，核质运输的知识很大程度上基于对病毒蛋白的开创性研究，这些研究使得能够鉴定出负责通过核孔进行易化运输的首批序列。对病毒蛋白的研究还促成了几种核质调控机制的发现，其中最具特征的是通过磷酸化作用。最近对磷酸化调节重要人类病原体（如人巨细胞病毒、登革病毒和呼吸道合胞病毒）编码的关键病毒基因产物的核输入和输出机制的描述，对抗病毒治疗学的发展具有重要意义。特别是，开发特异性和有效的激酶抑制剂使得通过抑制病毒基因产物核运输的磷酸化依赖性调节来阻断病毒感染的想法成为现实。此外，对一种鸡贫血病毒（CAV）蛋白的研究表明，该蛋白能够在磷酸化的特异性调控下选择性地靶向肿瘤细胞而非正常细胞的细胞核，这为癌细胞特异性核靶向开辟了令人兴奋的可能性。因此，对核质运输的研究不仅可能促成新的抗病毒方法的开发，还可能有助于抗癌策略的制定。
