Mutational antigenic landscape of prevailing H9N2 influenza virus hemagglutinin spectrum
Jiahao Zhang,
Xiaomin Wang,
Yiqun Chen,
Hejia Ye,
Shiping Ding,
Tao Zhang,
Yi Liu,
Huanan Li,
Lihong Huang,
Wenbao Qi,
Ming Liao
Affiliations
Jiahao Zhang
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Xiaomin Wang
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Yiqun Chen
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Hejia Ye
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China
Shiping Ding
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Tao Zhang
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Yi Liu
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Huanan Li
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Lihong Huang
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China
Wenbao Qi
State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China; Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China; Corresponding author
Ming Liao
National Avian Influenza Para-Reference Laboratory, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China; Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China; Corresponding author
Summary: H9N2 influenza viruses are globally endemic in birds, and a sharp increase in human infections with H9N2 occurred during 2021 to 2022. In this study, we assess the antigenic and pathogenic impact of 23 hemagglutinin (HA) amino acid mutations. Our study reveals that three specific mutations, labeled R164Q, N166D, and I220T, are responsible for the binding of antibodies with escape mutations. Variants containing R164Q and I220T mutations increase viral replication in avian and mammalian cells. Furthermore, T150A and I220T mutations are found to enhance viral replication in mice, indicating that these mutations may have the potential to adapt mammals. Structure analysis reveals that residues 164 and 220 bearing R164Q and I220T mutations increase interactions with the surrounding residues. Our findings enrich current knowledge about the risk assessment regarding which predominant HA immune-escape mutations of H9N2 viruses may pose the greatest threat to the emergence of pandemics in birds and humans.
