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研究揭示流感病毒聚合酶PB1亚基的高活性

2011/12/08 来源:科学网
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国际病毒学期刊Journal of General Virology于网络版在线发表了中国科学院上海巴斯德研究所孙兵研究组的最新研究成果。该研究揭示了流感病毒聚合酶PB1亚基对病毒跨种传播的重要作用。

流感病毒PB1亚基及其473位缬氨酸和598位脯氨酸对流感病毒复制能力的提升作用。(A)病毒空斑实验,(B,C)病毒在MDCK和A549细胞中的生长曲线

11月16日,国际病毒学期刊Journal of General Virology于网络版在线发表了中国科学院上海巴斯德研究所孙兵研究组的最新研究成果。该研究揭示了流感病毒聚合酶PB1亚基对病毒跨种传播的重要作用。

近年来,几次流感病毒的大流行造成了世界范围内的恐慌和损失,深入揭示流感病毒跨种传播的机制是预防和监控流感疫情的前提。上海巴斯德所分子病毒学组的研究人员通过对一株禽流感病毒聚合酶亚基PB1的研究,发现感染人的流感病毒的PB1亚基普遍具有更强的聚合酶活性;进一步研究发现,PB1亚基473位缬氨酸和598位脯氨酸与这种较强的聚合酶活性有关,而流感病毒聚合酶对病毒的复制以及mRNA的转录有至关重要的作用。

这个发现对理解数次流感大流行爆发的原因,以及流感疫情的监控有一定的帮助。

此项研究得到了欧盟第六框架计划、科技部、国家自然科学基金、中国科学院项目基金、上海巴斯德健康研究基金会、李嘉诚基金会等资助。

 

Amino acids 473V and 598P of PB1 from an avian origin influenza A virus contribute to polymerase activity especially in mammalian cells

Chen Xu, Wei-Bin Hu, Ke Xu, Bing Sun

It has been reported that the avian-origin PB1 protein (avian PB1) enhances influenza A virus polymerase activity in mammalian cells when it replaces the human-origin PB1 protein (human PB1). Characterization of the amino acid residues that contribute to this enhancement is needed. In this study, we found that PB1 protein from an avian origin influenza A virus (A/Cambodia/P0322095/2005, H5N1 [Cam]) could enhance the polymerase activity of an attenuated human isolated virus A/WSN/33 carrying the PB2 K627E mutation (WSN627E) in vitro. Furthermore, we identified 473 valine (V) and 598 proline (P) in the Cam PB1 as the residues responsible for this enhanced activity. Results from recombinant virus experiments demonstrate the contribution of PB1 amino acids 473V and 598P to polymerase activity in mammalian cells and in mice. Interestingly, the 473V is conserved in pH1N1 viruses from the 2009 pandemic. Substitution of the 473V by Leucine (L) in pH1N1 PB1 led to a decreased viral polymerase activity and a lower growth rate in mammalian cells, suggesting that PB1 amino acid 473V also plays a role in maintaining efficient viral replication of the pH1N1 virus. Thus, we conclude that two amino acids in avian-origin PB1, 473V and 598P, contribute to the polymerase activity of the H5N1 virus especially in mammalian cells, and that 473V in PB1 also contributes to efficient replication of the pH1N1 strain.

文献链接:http://vir.sgmjournals.org/content/early/2011/11/10/vir.0.036434-0.abstract

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