A novel influenza virus of the H7N9 subtype has infected more than 350 people in China since 19 February 2013. Evolutionary analysis indicates that the virus is a reassortant originated from H7, N9 and H9N2 avian influenza viruses, and bears some amino acids associated with mammalian receptor binding, raising concern over the possibility of a new influenza pandemic. Besides HA and NA, the mutation of the polymerase is known to have an important role in virulence, host adaptation and transmissibility in mammalians. In this article, the annotation of the polymerase protein domain associated with molecular function has been highlighted, suggesting the combination of RNA polymerase of H7N9 viruses is still not stable for host adaptation. In addition, the mutation hallmarks in polymerase gene of H7N9 are compared, providing the potential determinants of the evolution in the H7N9 influenza A virus.
KeywordsDiversityRNA PolymeraseH7N9 Influenza A Virus
Chen, E., Chen, Y., Fu, L., Chen, Z., Gong, Z., Mao, H., Wang, D., Ni, M., Wu, P., Yu, Z., He, T., Li, Z., Gao, J., Liu, S., Shu, Y., Cowling, B., Xia, S. and Yu, H. (2013) Human Infection with Avian Influenza A(H7N9) Virus Re-Emerges in China in Winter 2013. Euro Surveillance, 18, pii: 20616.
Dai, C. and Jiang, M. (2013) Understanding H7N9 Avian Flu. BMJ, 346, Article ID: f2755. http://dx.doi.org/10.1136/bmj.f2755
Shi, B., Xia, S., Yang, G.J., Zhou, X.N. and Liu, J. (2013) Research Priorities in Modeling the Transmission Risks of H7N9 Bird Flu. Infectious Diseases of Poverty, 2, 8. http://dx.doi.org/10.1186/2049-9957-2-8
Wu, Y. and Gao, G.F. (2013) Compiling of Comprehensive Data of Human Infections with Novel Influenza A (H7N9) Virus. Frontiers of Medicine, 7, 275-276.
Xu, C., Havers, F., Wang, L., Chen, T., Shi, J., Wang, D., Yang, J., Yang, L., Widdowson, M.A. and Shu, Y. (2013) Monitoring Avian Influenza A(H7N9) Virus through National Influenza-Like Illness Surveillance, China. Emerging Infectious Diseases, 19, 1289-1292.
Cowling, B.J., Jin, L., Lau, E.H., Liao, Q., Wu, P., Jiang, H., Tsang, T.K., Zheng, J., Fang, V.J., Chang, Z., Ni, M.Y., Zhang, Q., Ip, D.K., Yu, J., Li, Y., Wang, L., Tu, W., Meng, L., Wu, J.T., Luo, H., Li, Q., Shu, Y., Li, Z., Feng, Z., Yang, W., Wang, Y., Leung, G.M. and Yu, H. (2013) Comparative Epidemiology of Human Infections with Avian Influenza A H7N9 and H5N1 Viruses in China: A Population-Based Study of Laboratory-Confirmed Cases. The Lancet, 382, 129-137. http://dx.doi.org/10.1016/S0140-6736(13)61171-X
Gao, R., Cao, B., Hu, Y., Feng, Z., Wang, D., Hu, W., Chen, J., Jie, Z., Qiu, H., Xu, K., Xu, X., Lu, H., Zhu, W., Gao, Z., Xiang, N., Shen, Y., He, Z., Gu, Y., Zhang, Z., Yang, Y., Zhao, X., Zhou, L., Li, X., Zou, S., Zhang, Y., Li, X., Yang, L., Guo, J., Dong, J., Li, Q., Dong, L., Zhu, Y., Bai, T., Wang, S., Hao, P., Yang, W., Zhang, Y., Han, J., Yu, H., Li, D., Gao, G.F., Wu, G., Wang, Y., Yuan, Z. and Shu, Y. (2013) Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. The New England Journal of Medicine, 368, 1888-1897. http://dx.doi.org/10.1056/NEJMoa1304459
Liu, D., Shi, W., Shi, Y., Wang, D., Xiao, H., Li, W., Bi, Y., Wu, Y., Li, X., Yan, J., Liu, W., Zhao, G., Yang, W., Wang, Y., Ma, J., Shu, Y., Lei, F. and Gao, G.F. (2013) Origin and Diversity of Novel Avian Influenza A H7N9 Viruses Causing Human Infection: Phylogenetic, Structural, and Coalescent Analyses. The Lancet, 381, 1926-1932. http://dx.doi.org/10.1016/S0140-6736(13)60938-1
Kageyama, T., Fujisaki, S., Takashita, E., Xu, H., Yamada, S., Uchida, Y., Neumann, G., Saito, T., Kawaoka, Y. and Tashiro, M. (2013) Genetic Analysis of Novel Avian A(H7N9) Influenza Viruses Isolated from Patients in China. Euro Surveillance, 18, 20453.
Zhang, Y., Zhang, Q., Gao, Y., He, X., Kong, H., Jiang, Y., Guan, Y., Xia, X., Shu, Y., Kawaoka, Y., Bu, Z. and Chen, H. (2012) Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus. Journal of Virology, 86, 9666-9674. http://dx.doi.org/10.1128/JVI.00958-12
Hulse-Post, D.J., Franks, J., Boyd, K., Salomon, R., Hoffmann, E., Yen, H.L., Webby, R.J., Walker, D., Nguyen, T.D. and Webster, R.G. (2007) Molecular Changes in the Polymerase Genes (PA and PB1) Associated with High Pathogenicity of H5N1 Influenza Virus in Mallard Ducks. Journal of Virology, 81, 8515-8524. http://dx.doi.org/10.1128/JVI.00435-07
Gao, Y., Zhang, Y., Shinya, K., Deng, G., Jiang, Y., Li, Z., Guan, Y., Tian, G., Li, Y., Shi, J., Liu, L., Zeng, X., Bu, Z., Xia, X., Kawaoka, Y. and Chen, H. (2009) Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host. PLoS Pathogens, 5, e1000709. http://dx.doi.org/10.1371/journal.ppat.1000709
Hatta, M., Gao, P., Halfmann, P. and Kawaoka, Y. (2001) Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses. Science, 293, 1840-1842. http://dx.doi.org/10.1126/science.1062882
Le, Q.M., Sakai-Tagawa, Y., Ozawa, M., Ito, M. and Kawaoka, Y. (2009) Selection of H5N1 Influenza Virus PB2 during Replication in Humans. Journal of Virology, 83, 5278-5281. http://dx.doi.org/10.1128/JVI.00063-09
Steel, J., Lowen, A.C., Mubareka, S. and Palese, P. (2009) Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N. PLoS Pathogens, 5, e1000252. http://dx.doi.org/10.1371/journal.ppat.1000252
Gonzalez, S. and Ortin, J. (1999) Distinct Regions of Influenza Virus PB1 Polymerase Subunit Recognize vRNA and cRNA Templates. The EMBO Journal, 18, 3767-3775. http://dx.doi.org/10.1093/emboj/18.13.3767
Gonzalez, S. and Ortin, J. (1999) Characterization of the Influenza Virus PB1 Protein Binding to Viral RNA: Two Separate Regions of the Protein Contribute to the Interaction Domain. Journal of Virology, 73, 631-637.
Chu, C., Fan, S., Li, C., Macken, C., Kim, J.H., Hatta, M., Neumann, G. and Kawaoka, Y. (2012) Functional Analysis of Conserved Motifs in Influenza Virus PB1 Protein. PLoS ONE, 7, e36113. http://dx.doi.org/10.1371/journal.pone.0036113
Perez, D.R. and Donis, R.O. (2001) Functional Analysis of PA Binding by Influenza A Virus PB1: Effects on Polymerase Activity and Viral Infectivity. Journal of Virology, 75, 8127-8136. http://dx.doi.org/10.1128/JVI.75.17.8127-8136.2001
Zamarin, D., Ortigoza, M.B. and Palese, P. (2006) Influenza A Virus PB1-F2 Protein Contributes to Viral Pathogenesis in Mice. Journal of Virology, 80, 7976-7983. http://dx.doi.org/10.1128/JVI.00415-06
Herfst, S., Schrauwen, E.J., Linster, M., Chutinimitkul, S., de Wit, E., Munster, V.J., Sorrell, E.M., Bestebroer, T.M., Burke, D.F., Smith, D.J., Rimmelzwaan, G.F., Osterhaus, A.D. and Fouchier, R.A. (2012) Airborne Transmission of Influenza A/H5N1 Virus between Ferrets. Science, 336, 1534-1541. http://dx.doi.org/10.1126/science.1213362
de Wit, E., Munster, V.J., van Riel, D., Beyer, W.E., Rimmelzwaan, G.F., Kuiken, T., Osterhaus, A.D. and Fouchier, R.A. (2010) Molecular Determinants of Adaptation of Highly Pathogenic Avian Influenza H7N7 Viruses to Efficient Replication in the Human Host. Journal of Virology, 84, 1597-1606. http://dx.doi.org/10.1128/JVI.01783-09
Desmet, E.A., Bussey, K.A., Stone, R. and Takimoto, T. (2013) Identification of the N-Terminal Domain of the Influenza Virus PA Responsible for the Suppression of Host Protein Synthesis. Journal of Virology, 87, 3108-3118. http://dx.doi.org/10.1128/JVI.02826-12
Hemerka, J.N., Wang, D., Weng, Y., Lu, W., Kaushik, R.S., Jin, J., Harmon, A.F. and Li, F. (2009) Detection and Characterization of Influenza A Virus PA-PB2 Interaction through a Bimolecular Fluorescence Complementation Assay. Journal of Virology, 83, 3944-3955. http://dx.doi.org/10.1128/JVI.02300-08
Song, M.S., Pascua, P.N., Lee, J.H., Baek, Y.H., Park, K.J., Kwon, H.I., Park, S.J., Kim, C.J., Kim, H., Webby, R.J., Webster, R.G. and Choi, Y.K. (2011) Virulence and Genetic Compatibility of Polymerase Reassortant Viruses Derived from the Pandemic (H1N1) 2009 Influenza Virus and Circulating Influenza A Viruses. Journal of Virology, 85, 6275-6286. http://dx.doi.org/10.1128/JVI.02125-10
Qi, X., Qian, Y.H., Bao, C.J., Guo, X.L., Cui, L.B., Tang, F.Y., Ji, H., Huang, Y., Cai, P.Q., Lu, B., Xu, K., Shi, C., Zhu, F.C., Zhou, M.H. and Wang, H. (2013) Probable Person to Person Transmission of Novel Avian Influenza A (H7N9) Virus in Eastern China, 2013: Epidemiological Investigation. British Medical Journal, 347, Article ID: f4752. http://dx.doi.org/10.1136/bmj.f4752
Wu, A., Su, C., Wang, D., Peng, Y., Liu, M., Hua, S., Li, T., Gao, G.F., Tang, H., Chen, J., Liu, X., Shu, Y., Peng, D., and Jiang, T.J. (2013) Sequential Reassortments Underlie Diverse Influenza H7N9 Genotypes in China. Cell Host & Microbe, 14, 446-452. http://dx.doi.org/10.1016/j.chom.2013.09.001
Plotkin, J.B. and Dushoff, J. (2003) Codon Bias and Frequency-Dependent Selection on the Hemagglutinin Epitopes of Influenza A Virus. Proceedings of the National Academy of Sciences of the United States of America, 100, 7152-7157. http://dx.doi.org/10.1073/pnas.1132114100
The Lancet Infectious Diseases (2013) A Proportionate Response to H7N9. The Lancet Infectious Diseases, 13, 465. http://dx.doi.org/10.1016/S1473-3099(13)70134-8
Naffakh, N., Massin, P., Escriou, N., Crescenzo-Chaigne, B. and van der Werf, S. (2000) Genetic Analysis of the Compatibility between Polymerase Proteins from Human and Avian Strains of Influenza A Viruses. Journal of General Virology, 81, 1283-1291.