Pathogenicity of two novel human-origin H7N9 highly pathogenic avian influenza viruses in chickens and ducks
Human infection by low-pathogenic avian influenza viruses of the H7N9 subtype was first reported in March 2013 in China. Subsequently, these viruses caused five outbreaks through September 2017. In the fifth outbreak, H7N9 virus possessing a multiple basic amino acid insertion in the cleavage site of hemagglutinin emerged and caused 4% of all human infections in that period. To date, H7N9 highly pathogenic avian influenza viruses (HPAIVs) have been isolated from poultry, mostly chickens, as well as the environment. To evaluate the relative infectivity of these viruses in poultry, chickens and ducks were subjected to experimental infection with two H7N9 HPAIVs isolated from humans, namely A/Guangdong/17SF003/2016 and A/Taiwan/1/2017. When chickens were inoculated with the HPAIVs at a dose of 106 50% egg infectious dose (EID50), all chickens died within 2–5 days after inoculation, and the viruses replicated in most of the internal organs examined. The 50% lethal doses of A/Guangdong/17SF003/2016 and A/Taiwan/1/2017 in chickens were calculated as 103.3 and 104.7 EID50, respectively. Conversely, none of the ducks inoculated with either virus displayed any clinical signs, and less-efficient virus replication and less shedding were observed in ducks compared to chickens. These findings indicate that chickens, but not ducks, are highly permissive hosts for emerging H7N9 HPAIVs.
The authors are grateful to the National Institute for Viral Disease Control and Prevention, CCDC, for kindly providing the A/Guangdong/17SF003/2016. The authors would also like to thank Enago (http://www.enago.jp) for the English language review.
This study was partially supported by the research project for improving food safety and animal health of the Ministry of Agriculture, Forestry and Fisheries of Japan.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
Ethical standard statement
All experimental and animal procedures were approved by the ethics committee of the National Institute of Animal Health, Japan.
- 1.World Health Organization. Influenza at the human-animal interface. Monthly risk assessment summary as of 28 May 2018. https://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_28_05_2018.pdf?ua=1. Accessed 16 Sept 2018.
- 2.EFSA (European Food Safety Authority), EFSA ECDC (European Centre for Disease Prevention and Control), EURL (European Reference Laboratory for Avian Influenza), Adlhoch C, Brouwer A, Kuiken T, Mulatti P, Smietanka K, Staubach C, Willeberg P, Barrucci F, Verdonck F (2018) Amato L and Baldinelli F (2018) Scientific report: avian influenza overview November 2017–February 2018. EFSA J 16(3):5240. https://doi.org/10.2903/j.efsa.2018.5240 Google Scholar
- 3.World Health Organization. Human infection with avian influenza A(H7N9) virus—update. Disease outbreak news of 17 February 2014. http://www.who.int/csr/don/2014_02_17/en/. Accessed 9 May 2018.
- 4.World Health Organization. Human infection with avian influenza A(H7N9) virus—Canada. Disease outbreak news of 1 February 2015. http://www.who.int/csr/don/01-february-2015-avian-influenza/en/. Accessed 9 May 2018.
- 5.Chinese National Influenza Center. Chinese influenza weekly report. http://www.chinaivdc.cn/cnic/en/Surveillance/WeeklyReport/201807/t20180706_183192.htm. Accessed 16 Sept 2018
- 6.World Health Organization. Human infection with avian influenza A(H7N9) virus—China. Disease outbreak news of 22 February 2017. http://www.who.int/csr/don/22-february-2017-ah7n9-china/en/. Accessed 9 May 2018.
- 7.Wang D, Yang L, Zhu W, Zhang Y, Zou S, Bo H, Gao R, Dong J, Huang W, Guo J, Li Z, Zhao X, Li X, Xin L, Zhou J, Chen T, Dong L, Wei H, Li X, Liu L, Tang J, Lan Y, Yang J, Shu Y (2016) Two outbreak sources of influenza A (H7N9) viruses have been established in China. J Virol 90:5561–5573. https://doi.org/10.1128/JVI.03173-15 CrossRefGoogle Scholar
- 8.Yang L, Zhu W, Li X, Chen M, Wu J, Yu P, Qi S, Huang Y, Shi W, Dong J, Zhao X, Huang W, Li Z, Zeng X, Bo H, Chen T, Chen W, Liu J, Zhang Y, Liang Z, Shi W, Shu Y, Wang D (2017) Genesis and spread of newly emerged highly pathogenic H7N9 avian viruses in mainland China. J Virol 91:e01277-17. https://doi.org/10.1128/jvi.01277-17 CrossRefGoogle Scholar
- 9.World Organisation for Animal Health. Update on highly pathogenic avian influenza in animals (Type H5 and H7). http://www.oie.int/en/animal-health-in-the-world/update-on-avian-influenza/. Accessed 16 Sept 2018
- 10.Chen J, Zhang J, Zhu W, Zhang Y, Tan H, Liu M, Cai M, Shen J, Ly H, Chen J (2017) First genome report and analysis of chicken H7N9 influenza viruses with poly-basic amino acids insertion in the hemagglutinin cleavage site. Sci Rep 7:9972. https://doi.org/10.1038/s41598-017-10605-6 CrossRefGoogle Scholar
- 11.Qi W, Jia W, Liu D, Li J, Bi Y, Xie S, Li B, Hu T, Du Y, Xing L, Zhang J, Zhang F, Wei X, Eden JS, Li H, Tian H, Li W, Su G, Lao G, Xu C, Xu B, Liu W, Zhang G, Ren T, Holmes EC, Cui J, Shi W, Gao GF, Liao M (2018) Emergence and adaptation of a novel highly pathogenic H7N9 Influenza virus in birds and humans from a 2013 human-infecting low-pathogenic ancestor. J Virol 92:e00921-17. https://doi.org/10.1128/jvi.00921-17 CrossRefGoogle Scholar
- 12.Quan C, Shi W, Yang Y, Yang Y, Liu X, Xu W, Li H, Li J, Wang Q, Tong Z, Wong G, Zhang C, Ma S, Ma Z, Fu G, Zhang Z, Huang Y, Song H, Yang L, Liu WJ, Liu Y, Liu W, Gao GF, Bi Y (2018) New threats of H7N9 influenza virus: the spread and evolution of highly and low pathogenic variants with high genomic diversity in Wave Five. J Virol. https://doi.org/10.1128/jvi.00301-18 Google Scholar
- 14.Watanabe T, Kiso M, Fukuyama S, Nakajima N, Imai M, Yamada S, Murakami S, Yamayoshi S, Iwatsuki-Horimoto K, Sakoda Y, Takashita E, McBride R, Noda T, Hatta M, Imai H, Zhao D, Kishida N, Shirakura M, de Vries RP, Shichinohe S, Okamatsu M, Tamura T, Tomita Y, Fujimoto N, Goto K, Katsura H, Kawakami E, Ishikawa I, Watanabe S, Ito M, Sakai-Tagawa Y, Sugita Y, Uraki R, Yamaji R, Eisfeld AJ, Zhong G, Fan S, Ping J, Maher EA, Hanson A, Uchida Y, Saito T, Ozawa M, Neumann G, Kida H, Odagiri T, Paulson JC, Hasegawa H, Tashiro M, Kawaoka Y (2013) Characterization of H7N9 influenza A viruses isolated from humans. Nature 501:551–555. https://doi.org/10.1038/nature12392 CrossRefGoogle Scholar
- 17.Shi J, Deng G, Kong H, Gu C, Ma S, Yin X, Zeng X, Cui P, Chen Y, Yang H, Wan X, Wang X, Liu L, Chen P, Jiang Y, Liu J, Guan Y, Suzuki Y, Li M, Qu Z, Guan L, Zang J, Gu W, Han S, Song Y, Hu Y, Wang Z, Gu L, Yang W, Liang L, Bao H, Tian G, Li Y, Qiao C, Jiang L, Li C, Bu Z, Chen H (2017) H7N9 virulent mutants detected in chickens in China pose an increased threat to humans. Cell Res 27:1409–1421. https://doi.org/10.1038/cr.2017 CrossRefGoogle Scholar
- 18.Food and Agriculture Organization of the United Nations. H7N9 situation update. http://www.fao.org/ag/againfo/programmes/en/empres/H7N9/Situation_update.html. Accessed 16 Sept 2018
- 19.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 GF, Wu G, Wang Y, Yuan Z, Shu Y (2013) Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368:1888–1897. https://doi.org/10.1056/NEJMoa1304459 CrossRefGoogle Scholar
- 23.Organization WHO (2002) WHO manual on animal influenza diagnosis and surveillance. WHO/CDS/CSR/ NCS/2002.5.Google Scholar
- 25.Ohuchi M, Ohuchi R, Feldmann A, Klenk HD (1997) Regulation of receptor binding affinity of influenza virus hemagglutinin by its carbohydrate moiety. J Virol 71:8377–8384Google Scholar
- 33.Hiono T, Okamatsu M, Yamamoto N, Ogasawara K, Endo M, Kuribayashi S, Shichinohe S, Motohashi Y, Chu D-H, Suzuki M (2016) Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission. Vet Microbiol 182:108–115CrossRefGoogle Scholar
- 34.Löndt BZ, Núñez A, Banks J, Alexander DJ, Russell C, Richard-Löndt AC, Brown IH (2010) The effect of age on the pathogenesis of a highly pathogenic avian influenza (HPAI) H5N1 virus in Pekin ducks (Anas platyrhynchos) infected experimentally. Influenza Other Respir Viruses 4:17–25CrossRefGoogle Scholar
- 37.U.S. Department of Agriculture, Animal and Plant Health Inspection Service. HPAI 2014/15 confirmed detections. https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/avian-influenza-disease/sa_detections_by_states/hpai-2014-2015-confirmed-detections. Accessed 10 May 2018.
- 39.Ministry of Environment, Government of Japan. Information on highly pathogenic influenza. https://www.env.go.jp/nature/dobutsu/bird_flu/index.html. Accessed 16 Sept 2018.