Abstract
The H5N8 avian influenza viruses have been widely circulating in wild birds and are responsible for the loss of over 33 million domestic poultry in Europe, Russia, Middle East, and Asia since January 2020. To monitor the invasion and spread of the H5N8 virus in China, we performed active surveillance by analyzing 317 wild bird samples and swab samples collected from 41,172 poultry all over the country. We isolated 22 H5N8 viruses from wild birds and 14 H5N8 viruses from waterfowls. Genetic analysis indicated that the 36 viruses formed two different genotypes: one genotype viruses were widely detected from different wild birds and domestic waterfowls; the other genotype was isolated from a whopper swan. We further revealed the origin and spatiotemporal spread of these two distinct H5N8 virus genotypes in 2020 and 2021. Animal studies indicated that the H5N8 isolates are highly pathogenic to chickens, mildly pathogenic in ducks, but have distinct pathotypes in mice. Moreover, we found that vaccinated poultry in China could be completely protected against H5N8 virus challenge. Given that the H5N8 viruses are likely to continue to spread in wild birds, vaccination of poultry is highly recommended in high-risk countries to prevent H5N8 avian influenza.
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Abolnik, C., Pieterse, R., Peyrot, B.M., Choma, P., Phiri, T.P., Ebersohn, K., Heerden, C.J., Vorster, A.A., Zel, G., Geertsma, P.J., et al. (2019). The incursion and spread of highly pathogenic avian influenza H5N8 clade 2.3.4.4 within south Africa. Avian Dis 63, 149–156.
Ayllon, J., Domingues, P., Rajsbaum, R., Miorin, L., Schmolke, M., Hale, B.G., and García-Sastre, A. (2014). A single amino acid substitution in the novel H7N9 influenza A virus NS1 protein increases CPSF30 binding and virulence. J Virol 88, 12146–12151.
Baek, Y.G., Lee, Y.N., Lee, D.H., Shin, J.I., Lee, J.H., Chung, D.H., Lee, E. K., Heo, G.B., Sagong, M., Kye, S.J., et al. (2021). Multiple reassortants of H5N8 clade 2.3.4.4b highly pathogenic avian influenza viruses detected in South Korea during the winter of 2020–2021. Viruses 13, 490.
Baele, G., Lemey, P., Bedford, T., Rambaut, A., Suchard, M.A., and Alekseyenko, A.V. (2012). Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty. Mol Biol Evol 29, 2157–2167.
Baele, G., Li, W.L.S., Drummond, A.J., Suchard, M.A., and Lemey, P. (2013). Accurate model selection of relaxed molecular clocks in bayesian phylogenetics. Mol Biol Evol 30, 239–243.
Chen, H., Li, Y., Li, Z., Shi, J., Shinya, K., Deng, G., Qi, Q., Tian, G., Fan, S., Zhao, H., et al. (2006). Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. J Virol 80, 5976–5983.
Cui, Y., Li, Y., Li, M., Zhao, L., Wang, D., Tian, J., Bai, X., Ci, Y., Wu, S., Wang, F., et al. (2020). Evolution and extensive reassortment of H5 influenza viruses isolated from wild birds in China over the past decade. Emerg Microbes Infects 9, 1793–1803.
Dalby, A.R., and Iqbal, M. (2015). The European and Japanese outbreaks of H5N8 derive from a single source population providing evidence for the dispersal along the long distance bird migratory flyways. PeerJ 3, e934.
Drummond, A.J., Rambaut, A., Shapiro, B., and Pybus, O.G. (2005). Bayesian coalescent inference of past population dynamics from molecular sequences. Mol Biol Evol 22, 1185–1192.
El-Shesheny, R., Kandeil, A., Mostafa, A., Ali, M.A., and Webby, R.J. (2021). H5 Influenza viruses in Egypt. Cold Spring Harb Perspect Med 11, a038745.
Fan, S., Deng, G., Song, J., Tian, G., Suo, Y., Jiang, Y., Guan, Y., Bu, Z., Kawaoka, Y., and Chen, H. (2009). Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology 384, 28–32.
FAO. (2021). H7N9 situation update. Available from URL: https://www.fao.org/ag/againfo/programmes/en/empres/H7N9/situation_update.html.
Gao, R., Cao, B., Hu, Y., Feng, Z., Wang, D., Hu, W., Chen, J., Jie, Z., Qiu, H., Xu, K., et al. (2013). Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368, 1888–1897.
Gao, Y., Zhang, Y., Shinya, K., Deng, G., Jiang, Y., Li, Z., Guan, Y., Tian, G., Li, Y., Shi, J., et al. (2009). Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog 5, e1000709.
Harfoot, R., and Webby, R.J. (2017). H5 influenza, a global update. J Microbiol 55, 196–203.
Hay, A.J., Zambon, M.C., Wolstenholme, A.J., Skehel, J.J., and Smith, M. H. (1986). Molecular basis of resistance of influenza A viruses to amantadine. J Antimicrob Chemother 18, 19–29.
He, G., Ming, L., Li, X., Song, Y., Tang, L., Ma, M., Cui, J., and Wang, T. (2021). Genetically divergent highly pathogenic avian influenza A (H5N8) viruses in wild birds, eastern China. Emerg Infect Dis 27, 2940–2943.
Hu, M., Yuan, S., Zhang, K., Singh, K., Ma, Q., Zhou, J., Chu, H., and Zheng, B.J. (2017). PB2 substitutions V598T/I increase the virulence of H7N9 influenza A virus in mammals. Virology 501, 92–101.
Jeong, J., Kang, H.M., Lee, E.K., Song, B.M., Kwon, Y.K., Kim, H.R., Choi, K.S., Kim, J.Y., Lee, H.J., Moon, O.K., et al. (2014). Highly pathogenic avian influenza virus (H5N8) in domestic poultry and its relationship with migratory birds in South Korea during 2014. Vet MicroBiol 173, 249–257.
Jiao, P., Tian, G., Li, Y., Deng, G., Jiang, Y., Liu, C., Liu, W., Bu, Z., Kawaoka, Y., and Chen, H. (2008). A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 82, 1146–1154.
Khalil, A.M., Fujimoto, Y., Kojima, I., Esaki, M., Ri, K., Masatani, T., Matsui, T., and Ozawa, M. (2021). Genetic characterization of H5N8 highly pathogenic avian influenza viruses isolated from falcated ducks and environmental water in Japan in November 2020. Pathogens 10, 171.
Kim, Y.I., Park, S.J., Kwon, H.I., Kim, E.H., Si, Y.J., Jeong, J.H., Lee, I.W., Nguyen, H.D., Kwon, J.J., Choi, W.S., et al. (2017). Genetic and phylogenetic characterizations o fa novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea. Infect Genet Evol 53, 56–67.
Kong, H., Ma, S., Wang, J., Gu, C., Wang, Z., Shi, J., Deng, G., Guan, Y., and Chen, H. (2019). Identification of key amino acids in the PB2 and M1 proteins of H7N9 influenza virus that affect its transmission in Guinea pigs. J Virol 94, e01180–19.
Lee, D.H., Torchetti, M.K., Winker, K., Ip, H.S., Song, C.S., and Swayne, D.E. (2015). Intercontinental spread of Asian-origin H5N8 to North America through Beringia by migratory birds. J Virol 89, 6521–6524.
Lewis, N.S., Banyard, A.C., Whittard, E., Karibayev, T., Al Kafagi, T., Chvala, I., Byrne, A., Meruyert (Akberovna), S., King, J., Harder, T., et al. (2021). Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020. Emerg Microbes Infects 10, 148–151.
Li, C., Bu, Z., and Chen, H. (2014). Avian influenza vaccines against H5N1 ‘bird flu’. Trends Biotechnol 32, 147–156.
Li, X., Cui, P., Zeng, X., Jiang, Y., Li, Y., Yang, J., Pan, Y., Gao, X., Zhao, C., Wang, J., et al. (2019). Characterization of avian influenza H5N3 reassortants isolated from migratory waterfowl and domestic ducks in China from 2015 to 2018. Transbound Emerg Dis 66, 2605–2610.
Li, X., Lv, X., Li, Y., Peng, P., Zhou, R., Qin, S., Ma, E., Liu, W., Fu, T., Ma, P., et al. (2021). Highly pathogenic avian influenza A(H5N8) virus in swans, China, 2020. Emerg Infect Dis 27, 1732–1734.
Li, Y., Shi, J., Zhong, G., Deng, G., Tian, G., Ge, J., Zeng, X., Song, J., Zhao, D., Liu, L., et al. (2010). Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry, and humans in China from 2004 to 2009. J Virol 84, 8389–8397.
Li, Z., Jiang, Y., Jiao, P., Wang, A., Zhao, F., Tian, G., Wang, X., Yu, K., Bu, Z., and Chen, H. (2006). The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol 80, 11115–11123.
Liu, J., Xiao, H., Lei, F., Zhu, Q., Qin, K., Zhang, X.W., Zhang, X.L., Zhao, D., Wang, G., Feng, Y., et al. (2005). Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 309, 1206.
Liu, L., Zeng, X., Chen, P., Deng, G., Li, Y., Shi, J., Gu, C., Kong, H., Suzuki, Y., Jiang, Y., et al. (2016). Characterization of clade 7.2 H5 avian influenza viruses that continue to circulate in chickens in China. J Virol 90, 9797–9805.
Ma, S., Zhang, B., Shi, J., Yin, X., Wang, G., Cui, P., Liu, L., Deng, G., Jiang, Y., Li, C., et al. (2020). Amino acid mutations A286V and T437M in the nucleoprotein attenuate H7N9 viruses in mice. J Virol 94, e01530–19.
MARA. (2020). Bulletin of Ministry of Agriculture and Rural Affairs of China. No. 314. Available from URL: http://www.moa.gov.cn/gov-public/xmsyj/202007/t20200721_6348991.htm.
Napp, S., Majó, N., Sánchez-Gónzalez, R., and Vergara-Alert, J. (2018). Emergence and spread of highly pathogenic avian influenza A(H5N8) in Europe in 2016–2017. Transbound Emerg Dis 65, 1217–1226.
Neumann, G., and Kawaoka, Y. (2006). Host range restriction and pathogenicity in the context of influenza pandemic. Emerg Infect Dis 12, 881–886.
Olsen, B., Munster, V.J., Wallensten, A., Waldenstrom, J., Osterhaus, A.D.M.E., and Fouchier, R.A.M. (2006). Global patterns of influenza a virus in wild birds. Science 312, 384–388.
Pyankova, O.G., Susloparov, I.M., Moiseeva, A.A., Kolosova, N.P., Onkhonova, G.S., Danilenko, A.V., Vakalova, E.V., Shendo, G.L., Nekeshina, N.N., Noskova, L.N., et al. (2021). Isolation of clade 2.3.4.4b A(H5N8), a highly pathogenic avian influenza virus, from a worker during an outbreak on a poultry farm, Russia, December 2020. Eurosurveillance 26, 2100439.
Rodriguez-Morales, A.J., Bonilla-Aldana, D.K., and Paniz-Mondolfi, A.E. (2021). Concerns about influenza H5N8 outbreaks in humans and birds: facing the next airborne pandemic? Travel Med Infect Dis 41, 102054.
Selim, A.A., Erfan, A.M., Hagag, N., Zanaty, A., Samir, A.H., Samy, M., Abdelhalim, A., Arafa, A.S.A., Soliman, M.A., Shaheen, M., et al. (2017). Highly pathogenic avian influenza virus (H5N8) clade 2.3.4.4 infection in migratory birds, Egypt. Emerg Infect Dis 23, 1048–1051.
Shapiro, B., Rambaut, A., and Drummond, A.J. (2006). Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences. Mol Biol Evol 23, 7–9.
Shi, J., Deng, G., Kong, H., Gu, C., Ma, S., Yin, X., Zeng, X., Cui, P., Chen, Y., Yang, H., et al. (2017). H7N9 virulent mutants detected in chickens in China pose an increased threat to humans. Cell Res 27, 1409–1421.
Shi, J., Deng, G., Ma, S., Zeng, X., Yin, X., Li, M., Zhang, B., Cui, P., Chen, Y., Yang, H., et al. (2018). Rapid evolution of H7N9 highly pathogenic viruses that emerged in China in 2017. Cell Host Microbe 24, 558–568.e7.
Shin, D.L., Siebert, U., Lakemeyer, J., Grilo, M., Pawliczka, I., Wu, N.H., Valentin-Weigand, P., Haas, L., and Herrler, G. (2019). Highly pathogenic avian influenza A(H5N8) virus in gray seals, Baltic Sea. Emerg Infect Dis 25, 2295–2298.
Wang, W., Lu, B., Zhou, H., Suguitan Jr., A.L., Cheng, X., Subbarao, K., Kemble, G., and Jin, H. (2010). Glycosylation at 158N of the hemagglutinin protein and receptor binding specificity synergistically affect the antigenicity and immunogenicity of a live attenuated H5N1 A/Vietnam/1203/2004 vaccine virus in ferrets. J Virol 84, 6570–6577.
WHO. (2008). Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 14, e1.
WHO. (2011). Manual for the laboratory diagnosis and virological surveillance of influenza. Available from URL: https://apps.who.int/iris/handle/10665/44518.
Xiong, J., Zhou, H., Fan, L., Zhu, G., Li, Y., Chen, G., Zhang, J., Li, J., Zheng, H., Feng, W., et al. (2021). Emerging highly pathogenic avian influenza (H5N8) virus in migratory birds in Central China, 2020. Emerg Microbes Infects 10, 1503–1506.
Yang, L., Zhu, W., Li, X., Chen, M., Wu, J., Yu, P., Qi, S., Huang, Y., Shi, W., Dong, J., et al. (2017). Genesis and spread of newly emerged highly pathogenic H7N9 avian viruses in mainland China. J Virol 91, e01277–17.
Yang, Z.Y., Wei, C.J., Kong, W.P., Wu, L., Xu, L., Smith, D.F., and Nabel, G.J. (2007). Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science 317, 825–828.
Yin, X., Deng, G., Zeng, X., Cui, P., Hou, Y., Liu, Y., Fang, J., Pan, S., Wang, D., Chen, X., et al. (2021). Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China. PLoS Pathog 17, e1009561.
Zeng, X., Tian, G., Shi, J., Deng, G., Li, C., and Chen, H. (2018). Vaccination of poultry successfully eliminated human infection with H7N9 virus in China. Sci China Life Sci 61, 1465–1473.
Zeng, X., Chen, X., Ma, S., Wu, J., Bao, H., Pan, S., Liu, Y., Deng, G., Shi, J., Chen, P., et al. (2020). Protective efficacy of an H5/H7 trivalent inactivated vaccine produced from Re-11, Re-12, and H7-Re2 strains against challenge with different H5 and H7 viruses in chickens. J Integr Agr 19, 2294–2300.
Zhu, Q., Yang, H., Chen, W., Cao, W., Zhong, G., Jiao, P., Deng, G., Yu, K., Yang, C., Bu, Z., et al. (2008). A naturally occurring deletion in its NS gene contributes to the attenuation of an H5N1 swine influenza virus in chickens. J Virol 82, 220–228.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (31521005, 31672593), the Laboratory for Lingnan Modern Agriculture Project (NT2021007), the National Key Research and Development Program of China (2016YFD0500201), and the China Agriculture Research System (CARS-41G12). We thank the authors and submitting laboratories of the sequences from the GISAID EpiFlu Database.
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Cui, P., Zeng, X., Li, X. et al. Genetic and biological characteristics of the globally circulating H5N8 avian influenza viruses and the protective efficacy offered by the poultry vaccine currently used in China. Sci. China Life Sci. 65, 795–808 (2022). https://doi.org/10.1007/s11427-021-2025-y
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DOI: https://doi.org/10.1007/s11427-021-2025-y