"HTML" (The Lancet Microbe) recently published a study on the traceability and evolution analysis of human infection with H3N8 avian influenza virus led by Professor Liu Jinhua's team. It conducted a systematic study on the pathogenic characteristics and virus tracing of human infection with H3N8 subtype avian influenza virus, elucidating the origin, gene evolution and transmission process of the new H3N8 avian influenza virus, and revealed the risk of cross-species transmission of H3N8 virus. The research was jointly completed by China Agricultural University, Hunan Provincial Center for Disease Control and Prevention, Institute of Microbiology, Chinese Academy of Sciences, Chinese Center for Disease Control and Prevention, and other units.
Article Interpretation
Research Background
Avian influenza virus is not only the most serious infectious disease to poultry farming industry, but also can infect humans across species. It is an important zoonotic infectious disease. Since the first reported human infection with H5N1 avian influenza virus in 1997, various subtypes of avian influenza viruses such as H7N9, H5N6, H9N2, H10N8, and H10N3 have successively occurred [1-3]. In April 2022, human infection of H3N8 subtype avian influenza has successively occurred in Henan Province and Hunan Province, China. The H3N8 subtype influenza virus has infected a wide range of hosts. It has been isolated in animals such as avian, horse, dog, pig, seal, etc., and human infection is the first time [4]. Therefore, it is of great significance to master the clinical incidence characteristics of this new avian influenza virus infecting people, clarify the virus's generation and evolution process, and evaluate the risk of cross-species transmission of the virus to prevent and control the occurrence of this disease.
Research Methods
This study analyzed the clinical onset characteristics of cases in Changsha City, Hunan Province, investigated the activity environment before onset, and conducted environmental sampling of live poultry markets around the patient's residence. In order to trace the source of the virus, a systematic analysis of the H3N8 subtype avian influenza virus monitored in poultry in different regions of China between January 2021 and April 2022. In order to evaluate the public health risks of this new 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.
Research results
(1) The novel H3N8 virus infects people is a "spillary infection" event
The case in Changsha City, Hunan Province is a 5-year-old child patient with nasal congestion, cough, fever, and other typical influenza-like symptoms , and no serious symptoms such as pneumonia were found. The high-throughput sequencing technology was used to detect oropharyngeal swabs of patients with and identify them as a novel H3N8 virus infection. The patient had visited the market around his residence before the onset of the disease, and there were live poultry trading stalls in the market. Researchers detected positive samples of H3N8 virus in the live poultry and the environment in the live poultry stalls, indicating that the poisonous live poultry may be a source of infection. showed through serological monitoring that poultry practitioners in Henan and Hunan provinces did not detect H3N8 positive antibodies, indicating that this new H3N8 virus infects people is a typical "spillary infection" event and does not yet have the ability to continuously transmit interpersonal interpersonality.
(2) Traceability and Virus Evolution Analysis of the New H3N8 Virus
Animal Influenza Research Team of China Agricultural University found through a retrospective investigation that the new H3N8 virus was first monitored in chicken flocks in Guangdong Province in December 2021, and subsequently found in chicken flocks in many provinces in southern China. Through whole gene sequencing analysis of human and chicken H3N8 viruses, it was shown that the new H3N8 virus consists of three-source rearrangements of the internal genes of Eurasian avian branch H3 gene, North American avian branch N8 gene and G57 genotype H9N2 virus (Figure 1). The research team discovered in the early stage that the dominant prevalence of the G57 genotype H9N2 virus in Chinese chickens led to the production of the H7N9 avian influenza virus in 2013 (PNAS, 2013). The subsequent H10N8, H10N3, some H5N6, and the H3N8 virus found this time all contain the internal genes of the G57 genotype H9N2 virus, indicating that the G57 genotype H9N2 virus has become the "maternal virus" that produces the new influenza virus by providing internal genes.It is particularly worth noting that during the transmission of H3N8 virus, the composition of surface genes (HA, NA) is relatively stable, while the internal genes form multiple different evolutionary branches, indicating that there is a dynamic rearrangement between H3N8 virus and H9N2 virus (Figure 1), which is more conducive to the virus to quickly adapt to the breeding environment in different regions and is very likely to become popular in chickens. Therefore, blocking human infection with H3N8 virus is not only necessary to control the epidemic of H3N8 in poultry, but also to control the epidemic of H9N2 avian influenza virus in poultry and prevent the production of new avian influenza virus.
Figure 1. Generation process and gene evolution of 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 viruses. The study found that the novel H3N8 virus has both avian and human bireceptor binding (Figure 2. A). Gene analysis shows that the receptor binding regions of the chicken source and Hunan human H3N8 virus (A/Changsha/1000/2022) monitored in the study are still typical avian influenza virus characteristics, while the HA protein receptor binding region of Henan Province human H3N8 virus (A/Henan/4-10/2022) has an merger base at the 228th position of the HA protein receptor binding region, which can encode two amino acids , glutamate (G) and serine (S), and the serine residue at 228 is a typical feature of human influenza virus (Figure 2. C). crystal structure simulation shows that the HA protein G228S variant is more conducive to the binding of influenza viruses to α-2,6 sialic glycoside receptors, which is conducive to the virus's cross-species infection of humans, indicating that the novel H3N8 avian influenza virus can rapidly occur after infecting humans (Figure 2. B). The 1968 Hong Kong pandemic in human history was caused by the H3 subtype avian influenza virus, so we need 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 receptors
Conclusion
This study analyzed the pathogenic characteristics of H3N8 subtype avian influenza virus infection, the origin, evolution and cross-species transmission risks of H3N8 subtype avian influenza virus, which will help people to understand this new H3N8 avian influenza virus and formulate corresponding prevention and control measures. At the same time, research has also proved that the genetic rearrangement between the influenza virus and the avian influenza virus is an important way to produce new influenza viruses. Therefore, avoiding contact with wild birds and improving poultry breeding models is an important measure to control the production of new influenza viruses from the source. END
Animal Influenza Research Team of China Agricultural University was led by Professor Liu Jinhua. The team is based on animal influenza and its public health as the core research content, and is guided by serving society and industry and solving practical application problems. It carries out research on animal influenza epidemiology, pathogenic and cross-species transmission mechanisms, and new vaccine research and development. The team relies on the School of Veterinary Medicine of China Agricultural University, and has research platforms such as the key laboratories for the prevention and control of major poultry diseases such as avian influenza in the Ministry of Agriculture and Rural Affairs, the key laboratory of animal epidemiology of the Ministry of Agriculture and Rural Affairs, and the third-level biosafety laboratory of China Agricultural University. It has successively undertaken major projects, key projects of the National Natural Science Foundation, the National Key R&D Plan and other national projects. References
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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. http://www.nhc.gov.cn/yjb/s3578/202204/8dbeadf0efed45b0b2ea22928523e289.shtml
* Chinese interpretation is provided by the author and is for reference only. All content shall prevail.
