The first case of human infection with H3N8 subtype avian influenza virus was traced to its origin and evolution

The Lancet Microbe recently published a research led by Professor Liu Jinhua of China Agricultural University on the traceability and evolution analysis of human infection with H3N8 avian influenza virus, which systematically studied the pathogenic characteristics and virus traceability of H3N8 subtype avian influenza virus infecting human, clarified the origin, genetic evolution and transmission process of the new H3N8 avian influenza virus, and revealed the risk of cross species transmission of H3N8 virus. The study was jointly completed by China Agricultural University, Hunan Provincial Center for Disease Control and Prevention, Institute of Microbiology, Chinese Academy of Sciences, China Center for Disease Control and Prevention and other units.

Research background

Avian influenza virus is not only the most serious infectious disease to poultry breeding industry, but also can infect humans across species. It is an important zoonotic infectious disease. Since the first report of human infection with H5N1 avian influenza virus in 1997, there have been incidents of human infection with various subtypes of avian influenza viruses, such as H7N9, H5N6, H9N2, H10N8, and H10N3 [1-3]. In April 2022, Henan Province and Hunan Province in China have witnessed cases of human infection with H3N8 subtype avian influenza. H3N8 subtype influenza virus has a wide range of infection hosts. It was previously isolated from birds, horses, dogs, pigs, seals and other animals, and it is the first time that human infection has occurred [4]. Therefore, it is of great significance to master the clinical characteristics of this new type of avian influenza virus infecting humans, clarify the generation and evolution process of the virus, and evaluate the risk of cross species transmission of the virus for the prevention and control of this disease.

Research method

This study analyzed the clinical characteristics of the cases in Changsha, Hunan Province, investigated the activity environment of the patients before the onset, and sampled the environment of the live poultry market around the patient's residence. In order to trace the origin of the virus, the H3N8 subtype avian influenza virus detected in poultry in different regions of China from January 2021 to April 2022 was systematically analyzed. In order to evaluate the public health risk of this new type of avian influenza virus, the receptor binding and receptor domain structure of the virus were studied, and serum tests were carried out for poultry practitioners in Henan and Hunan provinces.

Figure 1. Production process and genetic evolution of the new H3N8 avian influenza virus

(3) Public health risks and warnings of new H3N8 virus

Receptor binding is a key determinant of the host range of influenza virus. It was found that the new H3N8 virus has the dual receptor binding property of bird and human (Fig. 2. A). Gene analysis showed that the receptor binding region of chicken origin and Hunan human origin H3N8 virus (A/Changsha/1000/2022) detected in the study was still typical of avian influenza virus, while the HA protein receptor binding region of Henan human origin H3N8 virus (A/Henan/4-10/2022) had a merger base at position 228, which could encode two amino acids, glutamate (G) and serine (S), of which the serine residue at position 228 was typical of human influenza virus (Figure 2 C）。 Crystal structure simulation shows that the variation of HA protein G228S is more beneficial to influenza virus and α- The binding of 2,6 sialyl glycoside receptors is conducive to the cross species infection of human virus, indicating that the new H3N8 avian influenza virus can rapidly undergo host adaptive variation after infecting human (Fig. 2. B). The 1968 Hong Kong pandemic influenza virus in human history was caused by H3 subtype avian influenza virus. Therefore, it is necessary to attach great importance to the threat of the new H3N8 avian influenza virus to public health.

Figure 2. Receptor binding analysis of H3N8 subtype avian influenza virus

This study analyzed the pathogenic characteristics, origin, evolution and cross species transmission risk of H3N8 subtype avian influenza virus infecting humans, which is helpful for people to understand this new H3N8 avian influenza virus and formulate corresponding prevention and control measures. At the same time, the research also proved that the gene rearrangement between migratory birds carrying influenza virus and poultry influenza virus has become an important way to produce new influenza viruses. Therefore, avoiding the contact between poultry and wild birds and improving the poultry breeding mode are important measures to control the generation of new influenza viruses from the source.

The Animal Influenza Research Team of China Agricultural University was established under the leadership of Professor Liu Jinhua. The team focuses on animal influenza and its public health, and focuses on serving society and industry and solving practical application problems. The team carries out research on animal influenza epidemiology, pathogenesis and cross species transmission mechanism, and new vaccine research and development. Relying on the School of Animal Medicine of China Agricultural University, the team has research platforms such as the Key Laboratory for the Prevention and Control of Avian Influenza and Other Major Poultry Diseases of the Ministry of Agriculture and Rural Affairs, the Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, and the Class III Laboratory of Biosafety of China Agricultural University. It has successively undertaken many national projects such as major projects and key projects of the National Natural Science Foundation of China, and national key research and development plans.

Reference

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3.Liu WJ Wu Y Bi Y et al.?Emerging HxNy influenza A viruses.Cold Spring Harb Perspect Med. 2022; 12a038406

4.?https://www.nhc.gov.cn/yjb/s3578/202204/8dbeadf0efed45b0b2ea22928523e289.shtml