Liu Jun, Huang Feng, Zhang Junsong, Tan Likai, Lu Gen, Zhang Xu, Zhang Hui
Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
Department of Respiration, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
Virus Genes. 2016 Jun;52(3):346-53. doi: 10.1007/s11262-016-1311-4. Epub 2016 Mar 15.
Human coinfection with a novel H7N9 influenza virus and the 2009 pandemic A(H1N1) influenza virus, H1N1pdm09, has recently been reported in China. Because reassortment can occur during coinfection, it is necessary to clarify the effects of gene reassortment between these two viruses. Among the viral ribonucleoprotein complex (vRNP) genes, only the PA gene of H1N1pdm09 enhances the avian influenza viral polymerase activity. Based on a phylogenetic analysis, we show a special evolutionary feature of the H1N1pdm09 PA gene, which clustered with those of the novel H7N9 virus and related H9N2 viruses, rather than in the outgroup as the H1N1pdm09 genes do on the phylogenetic trees of other vRNP genes. Using a minigenome system of the novel H7N9 virus, we further demonstrate that replacement of its PA gene significantly enhanced its polymerase activity, whereas replacement of the other vRNP genes reduced its polymerase activity. We also show that the residues of PA evolutionarily conserved between H1N1pdm09 and the novel H7N9 virus are associated with attenuated or neutral polymerase activity. The mutations associated with the increased activity of the novel H7N9 polymerase are characteristic of the H1N1pdm09 gene, and are located almost adjacent to the surface of the PA protein. Our results suggest that the novel H7N9 virus has more effective PB1, PB2, and NP genes than H1N1pdm09, and that H1N1pdm09-like PA mutations enhance the novel H7N9 polymerase function.
最近在中国报道了人类同时感染新型H7N9流感病毒和2009年甲型H1N1流感大流行病毒（H1N1pdm09）的情况。由于共感染期间可能发生基因重配，因此有必要阐明这两种病毒之间基因重配的影响。在病毒核糖核蛋白复合体（vRNP）基因中，只有H1N1pdm09的PA基因能增强禽流感病毒聚合酶活性。基于系统发育分析，我们展示了H1N1pdm09 PA基因的一种特殊进化特征，它与新型H7N9病毒及相关H9N2病毒的PA基因聚在一起，而不像在其他vRNP基因的系统发育树上那样，H1N1pdm09的基因位于外类群中。利用新型H7N9病毒的微型基因组系统，我们进一步证明，替换其PA基因会显著增强其聚合酶活性，而替换其他vRNP基因则会降低其聚合酶活性。我们还表明，H1N1pdm09和新型H7N9病毒之间进化上保守的PA残基与聚合酶活性减弱或呈中性有关。与新型H7N9聚合酶活性增加相关的突变具有H1N1pdm09基因的特征，且几乎位于PA蛋白表面附近。我们的结果表明，新型H7N9病毒具有比H1N1pdm09更有效的PB1、PB2和NP基因，且类似H1N1pdm09的PA突变增强了新型H7N9聚合酶的功能。
