11月16日,，國際病毒學期刊Journal of General Virology在線發(fā)表了中國科學院上海巴斯德研究所孫兵研究組的最新研究成果"Amino acids 473V and 598P of PB1 from an avian origin influenza A virus contribute to polymerase activity especially in mammalian cells",在文章中,，作者揭示了流感病毒聚合酶PB1亞基對病毒跨種傳播的重要作用。
近年來,，幾次流感病毒的大流行造成了世界范圍內(nèi)的恐慌和損失,，深入揭示流感病毒跨種傳播的機制是預防和監(jiān)控流感疫情的前提。上海巴斯德所分子病毒學組的研究人員通過對一株禽流感病毒聚合酶亞基PB1的研究,，發(fā)現(xiàn)感染人的流感病毒的PB1亞基普遍具有更強的聚合酶活性; 進一步研究發(fā)現(xiàn)PB1亞基473位纈氨酸和598位脯氨酸與這種較強的聚合酶活性有關,，而流感病毒聚合酶對病毒的復制以及mRNA的轉(zhuǎn)錄有至關重要的作用，這個發(fā)現(xiàn)對理解數(shù)次流感大流行爆發(fā)的原因,以及流感疫情的監(jiān)控有一定的幫助,。
此項研究得到了歐盟第六框架計劃,、科技部、國家自然科學基金,、中國科學院項目基金,、上海巴斯德健康研究基金會、李嘉誠基金會等資助,。(生物谷Bioon.com)
doi: 10.1099/vir.0.036434-0
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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, Yun-Xia He, Tong-Yan Wang, Ze Chen, Tian-Xian Li, Jin-Hua Liu, Philippe Buchy and 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.
