Abstract
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.
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Acknowledgments
We acknowledge the authors who submitted the influenza sequences used in this study to the GISAID EpiFlu and the NCBI GenBank Databases. We thank Dr. Mengfeng Li for providing the H1N1pdm09 virus. We are grateful to Dr. Robert Webster (St. Jude) for providing the pHW2000 plasmid for generating influenza minigenome system. We thank Dr. Janine Miller for her professional polishing on the language of this manuscript. This work was supported by the National Special Research Program for Important Infectious Diseases (No. 2013ZX10001004), Introduction of Innovative R&D Team Program of Guangdong Province (No. 2009010058), National Basic Research Program of China (973 Program) (No. 2010CB912202), and Natural Science Foundation of Guangdong (No. 9251008901000022).
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Jun Liu and Feng Huang have contributed equally to this work.
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Liu, J., Huang, F., Zhang, J. et al. Characteristic amino acid changes of influenza A(H1N1)pdm09 virus PA protein enhance A(H7N9) viral polymerase activity. Virus Genes 52, 346–353 (2016). https://doi.org/10.1007/s11262-016-1311-4
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DOI: https://doi.org/10.1007/s11262-016-1311-4