武大生科院6年研究 发PNAS文章

　　

生物通报道：武汉大学生命科学学院病毒学国家重点实验室，芬兰赫尔辛基大学（University of Helsinki） 的研究人员发现了SARS冠状病毒致命点：一组叫“非结构蛋白nsp14”的基因编码。这一研究成果公布在《PNAS》杂志上。

领导这一研究的是武大生科院郭德银教授，其2002年作为武汉大学“珞珈学者”特聘教授回国，主要研究领域包括RNA病毒（冠状病毒和丙肝病毒）的基因组复制和与宿主细胞相互作用的分子机理；病毒免疫逃逸的分子机制；基于RNA干扰（RNAi）的艾滋病毒基因治疗。

文章的其它作者包括博士生陈宇，田波院士等。

SARS病毒曾在我国广东爆发流行，并在较短时间内传播到30多个国家与地区，对人类生命健康和经济社会发展造成重大损失。近年来，国内外实验室对SARS病毒进行了大量研究工作，但对SARS病毒的发生特点和致病机制仍然知之甚少。SARS病毒虽然已得到控制，但自然界野生动物群体中还存在SARS样冠状病毒，SARS病毒再次爆发的危险依然存在。

就此武大生科院的研究人员展开了相关研究，据长江日报报道，陈宇表示，非典病毒是现在发现的最大的RNA（核糖核酸）病毒，也就是生命基因靠RNA传递，“非结构蛋白nsp14”是这个基因传递链条上至关重要的一节，不仅能够保证病毒不效复制，还给病毒加上一顶特殊的保护性“帽子”。

陈宇形象地解释，首先，它为病毒遗传信息乔装打扮，让免疫系统识别不出，采取“特洛伊木马战术”，不知不觉中将大量部队送入了要袭击的地方。 非典病毒的遗传信息是通过RNA传递的，很不稳定，容易降解，但这项“帽子”能起到保护作用。此外，它还是将其基因变成病毒生病蛋白的核心，没有这组编码，再多基因也变不成病毒。

谈及这一攻略的应用，郭德银说，它为筛选抗击非典病毒药物奠定了基础，比如可通过这个系统，找出某种对非典病毒这一功能有害、但对人体无害的物质，进而研发成小分子药物。

附：　　

郭德银

　　职称职务： 特聘教授，博导，副院长
　　出　生： 1965年4月于河南省
　　学　位： 博士
　　毕业学校： 联邦德国布伦瑞克理工大学
　　学科专业： 微生物学、病毒学、分子生物学
　
　　主要研究领域：
　　RNA病毒（冠状病毒和丙肝病毒）的基因组复制和与宿主细胞相互作用的分子机理；病毒免疫逃逸的分子机制；基于RNA干扰（RNAi）的艾滋病毒基因治疗。

　　代表性论文
　　1. Peng X, Pan J, Gong R, Liu Y, Kang S, Feng H, Qiu G, Guo D, Tien P, Xiao G.. (2006). Functional characterization of syncytin-A, a newly murine endogenous virus envelope protein: implication for its fusion mechanism. J Biol Chem. 2006 Nov 14; [Epub ahead of print].
　　2.Hussain Snawar, Ji’an Pan, Yu Chen, Yalin Yang, Jing Xu, Yu Peng, Ying Wu, Chaoyang Li, Ying Zhu, Po Tien, Deyin Guo*. (2005). Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. Journal of Virology 79:5288-95.
　　3. Zhaoyang Li, Yong Xiong, Yu Peng, Ji’an Pan, Yu Chen, Xiaoyun Wu, Snawar Hussain, Po Tien, Deyin Guo*. (2005). Specific inhibition of HIV-1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis. FEBS Lett. 579, 3100-6.
　　4. Zhu, Y., M. Liu, W. Zhao, J. Zhang, X. Zhang, K. Wang, C. Gu, K. Wu, Y. Li, C. Zheng, G. Xiao, H. Yan, J. Zhang, D. Guo, P. Tien, and J. Wu. (2005). Isolation of virus from a SARS patient and genome-wide analysis of genetic mutations related to pathogenesis and epidemiology from 47 SARS-CoV isolates. Virus Genes 30: 93-102.
　　5. Deyin Guo*, Carl Spetz, Mart Saarma & Jari Valkonen. (2003) Two plant proteins, including a novel RING-finger protein, interact with the potyviral multifunctional protein HC-Pro. Molecular Plant-Microbe Interactions 16, 405-410.
　　6. Deyin Guo*, Minna-Liisa Rajam?ki, Mart Saarma & Jari PT Valkonen. (2001). Towards a protein interaction map of potyviruses: protein interaction matrixes of two potyviruses based on the yeast two-hybrid system. Journal of General Virology 82, 935-939.
 

原文摘要：

Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase

The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3′-to-5′ exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.