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Literature detail

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

Jing Yang1,2,3 Juan Li4,5 Ju Sun1,3,6 Jiaming Li1,3 Guanghua Fu7 Tian Tian1,6 Yongchun Yang8 Xuancheng Lu9 Shan Li4,5 Lixia Wang1,6 Jia Dong1 Mingjia Wu1,2 Yun Liu1,6 Delong Li10 Dongfang Hu11 Hui Dong4 Ruoyu Shang1,5 Yanqing Wang1,2 Kunpeng Yuan1,6 Lin Ran1,2 Honglei Sun12 Wenxia Tian6 Yu Huang7 Jinhua Liu12 Wenjun Liu1,2 Weifeng Shi13,14 George F Gao15,16,17 Yuhai Bi18,19,20,21,22
Affiliations 22 institutions
  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. [email protected].
  14. Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  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. [email protected].
  16. University of Chinese Academy of Sciences, Beijing, China. [email protected].
  17. The D. H. Chen School of Universal Health, Zhejiang University, Hangzhou, China. [email protected].
  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. [email protected].
  19. University of Chinese Academy of Sciences, Beijing, China. [email protected].
  20. Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, China. [email protected].
  21. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. [email protected].
  22. Collaborative Innovation Center for Prevention and Control of Zoonoses, Jinzhou Medical University, Jinzhou, China. [email protected].
PMID 40461649 2025 Nat Microbiol eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

Genetic Variation Influenza A Virus, H9N2 Subtype Influenza in Birds Poultry Poultry Diseases Viral Zoonoses Zoonoses Animals Chickens China Ferrets Guinea Pigs Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Mutation Phylogeny

Structured evidence records

Evidence records

9 total
Host Range Experiment 3 records
Host Range Experiment Extraction confidence 0.90
Key finding

H9N2 avian influenza viruses with HA-L226 and NP-N52 mutations replicated more efficiently in human cells in vitro.

Virus
IAV H9N2
Location
Not specified
Supporting text

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.

Method
replication assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.90
Key finding

H9N2 viruses carrying HA-L226, PB2-V/K627, and NP-N52 were transmissible among guinea pigs and ferrets by direct contact and respiratory droplet.

Virus
IAV H9N2
Location
Not specified
Supporting text

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.

Method
transmission experiment
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 0.90
Key finding

H9N2 viruses carrying HA-L226, PB2-V/K627, and NP-N52 were transmissible among ferrets by direct contact and respiratory droplet.

Virus
IAV H9N2
Location
Not specified
Supporting text

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.

Method
transmission experiment
Experimental system
in vivo animal experiment
Genomic Evolution 2 records
Genomic Evolution Extraction confidence 0.90
Key finding

Phylogenetic analysis of H9N2 avian influenza viruses identified ten HA sub-subclades within the BJ94 lineage circulating in poultry in China.

Virus
IAV H9N2
Host
Aves
Location
Not specified
Supporting text

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.

Genes or proteins
HA
Analysis methods
phylogenetic analysis
Genomic Evolution Extraction confidence 0.90
Key finding

Genome analysis revealed that most H9N2 avian influenza viruses carried HA-L226 and NP-N52 mutations associated with human receptor binding and MxA resistance.

Virus
IAV H9N2
Host
Aves
Location
Not specified
Supporting text

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.

Genes or proteins
HA; NP
Analysis methods
sequence analysis
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.85
Key finding

H9N2 avian influenza viruses transmitted between guinea pigs and ferrets, indicating cross-species transmission among non-human mammals.

Virus
IAV H9N2
Location
Not specified
Supporting text

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.

Method
experimental infection
Study design
animal experiment
Transmission direction
animal-to-animal
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

H9N2 avian influenza viruses carrying HA-L226, PB2-V/K627, and NP-N52 mutations showed molecular adaptation for human-type receptor binding, MxA resistance, and increased replication and transmissibility in mammalian models.

Virus
IAV H9N2
Host
Not specified
Location
Not specified
Supporting text

H9N2 strains with HA-L226 and NP-N52 mutations preferred human-type receptors and increased replication in human cells in vitro, regardless 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.

Genes or proteins
HA; PB2; NP
Receptors
human-type receptors
Host factors
MxA
Mutations
HA-L226; PB2-V627; PB2-K627; NP-N52
Mechanism types
receptor_binding; replication_efficiency; polymerase_activity; immune_escape; transmission_fitness
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.90
Key finding

H9N2 avian influenza viruses possessing the HA-L226 mutation showed preferential binding to human-type receptors and enhanced replication in human cells, supporting receptor compatibility with human hosts.

Virus
IAV H9N2
Location
Not specified
Supporting text

H9N2 strains with HA-L226 and NP-N52 mutations preferred human-type receptors and increased replication in human cells in vitro.

Receptors
human-type receptors
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 0.95
Key finding

Nationwide surveillance of poultry in live markets across China detected H9N2 avian influenza viruses as the dominant subtype from 2019 to 2023 among 18,425 samples.

Virus
IAV H9N2
Host
Aves
Location
China China
Supporting text

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.

Geographic raw
China
Country inferred
China