Genetic diversity of H9N2 avian influenza viruses in poultry across China and implications for zoonotic transmission

Jing Yang^#^{1

2

3}, Juan Li^#^{4

5}, Ju Sun^#^{1

3

6}, Jiaming Li^#^{1

3}, Guanghua Fu^#⁷, Tian Tian^#^{1

6}, Yongchun Yang^#⁸, Xuancheng Lu⁹, Shan Li^{4

5}, Lixia Wang^{1

6}, Jia Dong¹, Mingjia Wu^{1

2}, Yun Liu^{1

6}, Delong Li¹⁰, Dongfang Hu¹¹, Hui Dong⁴, Ruoyu Shang^{1

5}, Yanqing Wang^{1

2}, Kunpeng Yuan^{1

6}, Lin Ran^{1

2}, Honglei Sun¹², Wenxia Tian⁶, Yu Huang⁷, Jinhua Liu¹², Wenjun Liu^{1

2}, Weifeng Shi^{13

14}, George F Gao^{15

16

17}, Yuhai Bi^{18

19

20

21

22}

Affiliations

¹ Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, China.
⁴ Key Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, China.
⁵ School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, China.
⁶ College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
⁷ Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou, China.
⁸ Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology and College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, China.
⁹ National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
¹⁰ College of Veterinary Medicine, Southwest University, Chongqing, China.
¹¹ College of Animal Science and Technology, Henan Institute of Science and Technology, Xinxiang, China.
¹² National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.
¹³ Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shiwf@ioz.ac.cn.
¹⁴ Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shiwf@ioz.ac.cn.
¹⁵ Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, China. gfgao@zju.edu.cn.
¹⁶ University of Chinese Academy of Sciences, Beijing, China. gfgao@zju.edu.cn.
¹⁷ The D. H. Chen School of Universal Health, Zhejiang University, Hangzhou, China. gfgao@zju.edu.cn.
¹⁸ Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, China. beeyh@im.ac.cn.
¹⁹ University of Chinese Academy of Sciences, Beijing, China. beeyh@im.ac.cn.
²⁰ Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, China. beeyh@im.ac.cn.
²¹ College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. beeyh@im.ac.cn.
²² Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, China. beeyh@im.ac.cn.

^# Contributed equally.

PMID: 40461649
DOI: 10.1038/s41564-025-02002-x

Genetic diversity of H9N2 avian influenza viruses in poultry across China and implications for zoonotic transmission

Jing Yang et al. Nat Microbiol. 2025 Jun.

. 2025 Jun;10(6):1378-1392.

doi: 10.1038/s41564-025-02002-x. Epub 2025 Jun 3.

Authors

Affiliations

¹ Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, China.
⁴ Key Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, China.
⁵ School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, China.
⁶ College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
⁷ Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou, China.
⁸ Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology and College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, China.
⁹ National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), Laboratory Animal Center, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
¹⁰ College of Veterinary Medicine, Southwest University, Chongqing, China.
¹¹ College of Animal Science and Technology, Henan Institute of Science and Technology, Xinxiang, China.
¹² National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.
¹³ Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shiwf@ioz.ac.cn.
¹⁴ Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shiwf@ioz.ac.cn.
¹⁵ Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, China. gfgao@zju.edu.cn.
¹⁶ University of Chinese Academy of Sciences, Beijing, China. gfgao@zju.edu.cn.
¹⁷ The D. H. Chen School of Universal Health, Zhejiang University, Hangzhou, China. gfgao@zju.edu.cn.
¹⁸ Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, China. beeyh@im.ac.cn.
¹⁹ University of Chinese Academy of Sciences, Beijing, China. beeyh@im.ac.cn.
²⁰ Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, China. beeyh@im.ac.cn.
²¹ College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. beeyh@im.ac.cn.
²² Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, China. beeyh@im.ac.cn.

^# Contributed equally.

PMID: 40461649
DOI: 10.1038/s41564-025-02002-x

Abstract

Nationwide surveillance of avian influenza viruses (AIVs) in live poultry markets across China has occurred since 2014, providing a resource for AIV prevalence and genetic diversity studies. Here we report that 3,237 of 18,425 samples from poultry were AIV positive (17.57%) between 2019 and 2023, with H9N2 being the dominant subtype. We developed an automated phylogeny-based nomenclature system to classify genetic clades of the dominant H9N2 lineage, the BJ94 lineage. Using this model, we found that ten haemagglutinin (HA) sub-subclades cocirculated in poultry and showed antigenic variation. In addition, 99.46% and 96.17% of H9N2 AIVs in 2021-2023 possessed human-receptor binding-related HA-L226 and human MxA-resistance-related NP-N52 mutations, respectively. H9N2 strains with these two mutations preferred human-type receptors and increased replication in human cells in vitro, regardless of the presence of PB2-V/K/E627. Moreover, H9N2 AIVs containing HA-L226, PB2-V/K627 and NP-N52 were transmitted from infected to naive guinea pigs and ferrets through direct contact and respiratory droplet. This highlights the potential zoonotic risks of H9N2 AIVs.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Bi, Y. et al. CASCIRE surveillance network and work on avian influenza viruses. Sci. China Life Sci. 60, 1386–1391 (2017). - PubMed
1. Bi, Y. et al. Genesis, evolution and prevalence of H5N6 avian influenza viruses in China. Cell Host Microbe 20, 810–821 (2016). - PubMed
1. Bi, Y. et al. Dominant subtype switch in avian influenza viruses during 2016–2019 in China. Nat. Commun. 11, 5909 (2020). - PubMed - PMC
1. Gao, G. F. Influenza and the live poultry trade. Science 344, 235 (2014). - PubMed
1. Shi, W. & Gao, G. F. Emerging H5N8 avian influenza viruses. Science 372, 784–786 (2021). - PubMed

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Genetic diversity of H9N2 avian influenza viruses in poultry across China and implications for zoonotic transmission

Affiliations

Genetic diversity of H9N2 avian influenza viruses in poultry across China and implications for zoonotic transmission

Authors

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Abstract

Conflict of interest statement

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