A型流感病毒是負鏈單鏈RNA病毒,，迄今為止已引起四次全球流感大流行。流感病毒具有很高變異性，第一年接種疫苗后,，一般第二年就需要重新接種新疫苗。目前針對流感病毒神經(jīng)氨酸酶 (Neuraminidase, NA）以及M2 離子通道的藥物均發(fā)現(xiàn)抗藥突變體,。因此,，深入理解和揭示A型流感病毒基因復(fù)制包括基因復(fù)制起始機制，對于尋找抗流感病毒的靶分子具有重要意義,。
中科院上海巴斯德研究所豐田哲也領(lǐng)導(dǎo)的研究組發(fā)現(xiàn)A型流感病毒從vRNA (viral RNA, vRNA )到cRNA (complementary RNA, cRNA)的復(fù)制是從vRNA 3’ 末端的第二位核苷酸殘基開始的,。他們證實，為了能夠復(fù)制完整cRNA,，病毒首先利用宿主核苷酸末端轉(zhuǎn)移酶在vRNA 3’ 末端添加核苷酸殘基,。他們的研究還發(fā)現(xiàn)，在cRNA到vRNA的復(fù)制過程中,，病毒首先在cRNA 3’ 端內(nèi)部序列開始合成ApG雙核苷酸RNA,； 然后，ApG雙核苷酸由于下游RNA空間結(jié)構(gòu)的限制轉(zhuǎn)移至cRNA 3’ 端與GpC配對引發(fā)復(fù)制延伸,。該研究不但揭示了病毒從vRNA到cRNA復(fù)制過程起始的機制,，而且更深入發(fā)現(xiàn)了cRNA到vRNA復(fù)制起始中ApG生成后轉(zhuǎn)移分子機理。
9月20日,，國際著名學(xué)術(shù)期刊Journal of Biological Chemistry在線發(fā)表了這項研究成果,，本研究由博士研究生張仕堅在豐田哲也的指導(dǎo)下完成。
該研究得到中國科學(xué)院知識創(chuàng)新工程重大項目,、國家自然科學(xué)基金,、李嘉誠基金會、歐盟第六框架項目 (FLUINNATE)的資助,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
