A型流感病毒是负链单链RNA病毒，迄今为止已引起四次全球流感大流行。流感病毒具有很高变异性，第一年接种疫苗后，一般第二年就需要重新接种新疫苗。目前针对流感病毒神经氨酸酶 (Neuraminidase, NA）以及M2 离子通道的药物均发现抗药突变体。因此，深入理解和揭示A型流感病毒基因复制包括基因复制起始机制，对于寻找抗流感病毒的靶分子具有重要意义。
中科院上海巴斯德研究所丰田哲也领导的研究组发现A型流感病毒从vRNA (viral RNA, vRNA )到cRNA (complementary RNA, cRNA)的复制是从vRNA 3’ 末端的第二位核苷酸残基开始的。他们证实，为了能够复制完整cRNA，病毒首先利用宿主核苷酸末端转移酶在vRNA 3’ 末端添加核苷酸残基。他们的研究还发现，在cRNA到vRNA的复制过程中，病毒首先在cRNA 3’ 端内部序列开始合成ApG双核苷酸RNA； 然后，ApG双核苷酸由于下游RNA空间结构的限制转移至cRNA 3’ 端与GpC配对引发复制延伸。该研究不但揭示了病毒从vRNA到cRNA复制过程起始的机制，而且更深入发现了cRNA到vRNA复制起始中ApG生成后转移分子机理。
9月20日，国际著名学术期刊Journal of Biological Chemistry在线发表了这项研究成果，本研究由博士研究生张仕坚在丰田哲也的指导下完成。
该研究得到中国科学院知识创新工程重大项目、国家自然科学基金、李嘉诚基金会、欧盟第六框架项目 (FLUINNATE)的资助。（生物谷Bioon.com）
生物谷推荐英文摘要：
JBC doi: 10.1074/jbc.R110.129809
Influenza Hemagglutinin and Neuraminidase Membrane Glycoproteins*
Steven J. Gamblin1 and John J. Skehel2
From the Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
Considerable progress has been made toward understanding the structural basis of the interaction of the two major surface glycoproteins of influenza A virus with their common ligand/substrate: carbohydrate chains terminating in sialic acid. The specificity of virus attachment to target cells is mediated by hemagglutinin, which acquires characteristic changes in its receptor-binding site to switch its host from avian species to humans. Anti-influenza drugs mimic the natural sialic acid substrate of the virus neuraminidase enzyme but utilize the much tighter binding of the drugs for efficacy. Resistance to one of the two main antiviral drugs is differentially acquired by the two distinct subsets of neuraminidase as a consequence of structural differences in the enzyme active site between the two phylogenetic groups.
