Novel H10N3 avian influenza viruses: a potential threat to public health

Novel H10N3 avian influenza viruses have been frequently isolated from poultry across various regions of China (including Jiangsu, Zhejiang, Fujian, and other provinces) in recent years and have caused two cases of confirmed human infection.1Qi X Qiu H Hao S et al.Human infection with an avian-origin influenza A (H10N3) virus.N Engl J Med. 2022; 386: 1087-1088Crossref PubMed Scopus (16) Google Scholar, 2Zhang W Zhang Z Wang M Pan X Jiang X Second identified human infection with the avian influenza virus H10N3: a case report.Ann Intern Med. 2023; 176: 429-431Crossref PubMed Scopus (0) Google Scholar, 3Zhang Y Shi J Cui P et al.Genetic analysis and biological characterization of H10N3 influenza A viruses isolated in China from 2014 to 2021.J Med Virol. 2023; 95e28476Google Scholar To prevent further human infection, an in-depth and systematic assessment of the pandemic risk of these viruses is essential. In this Correspondence, we report key findings from our investigation of the genomic and biological features of the H10N3 viruses isolated from humans and chickens. An influenza A virus (A/Jiangsu/428/2021) was isolated from a 41-year-old man in China, representing the first recorded case of human infection with H10N3.1Qi X Qiu H Hao S et al.Human infection with an avian-origin influenza A (H10N3) virus.N Engl J Med. 2022; 386: 1087-1088Crossref PubMed Scopus (16) Google Scholar During surveillance of live poultry markets in China from 2020 to 2022, we isolated 16 H10N3 viruses (appendix p 26). Phylogenetic analysis indicated that the haemagglutinin and neuraminidase genes belonged to the Eurasian lineage and formed a monophyletic group, suggesting a substantial evolutionary history of the novel H10N3 viruses before their detection (appendix pp 5, 11–12). The six internal genes originating from the H9N2 avian influenza A virus were grouped into multiple clusters and categorised into 15 genotypes (G0 to G14; appendix pp 5–6, 13–18, 33–34), suggesting that H10N3 viruses continue to evolve and undergo frequent reassortment. Such a persistent pattern of reassortment might enhance the fitness of avian influenza viruses in chickens and mammals, thereby posing a substantial threat to public health. We identified multiple amino acid residues related to adaptation in mammalian hosts in these novel H10N3 viruses (appendix pp 6–7, 27–32), and both human-derived and chicken-derived isolates showed high affinity for sialic acid-α-2,6-galactose receptors (appendix pp 7, 19). The human-derived H10N3 virus can replicate at high frequencies in various mouse organs, displaying high pathogenicity in mice, with a median lethal dose of 1·2 log10 of the 50% egg infective dose (appendix pp 7–8, 20–22). Notably, the human-derived isolate was not transmitted to guinea pigs via respiratory droplets (appendix pp 9, 23–24). However, the chicken-derived virus CK/0132/21 was highly pathogenic to mice, with a median lethal dose of 3·2 log10 of the 50% egg infective dose, and could be transmitted between guinea pigs via respiratory droplets (appendix pp 7–9, 20–24). These results indicated that some chicken-derived viruses might hold the potential to evolve into a pandemic threat in the human population, without the need for prior adaptation. The emergence of the novel H10N3 virus highlights the persistent and evolving threat posed by the diverse array of avian influenza viruses found in China. Given the occurrence of asymptomatic infections caused by these novel H10N3 viruses in chickens (appendix pp 9–10, 25), controlling their widespread propagation in poultry is a challenging task, especially when considering previous experiences with avian H9N2 viruses.4Bi Y Li J Shi W The time is now: a call to contain H9N2 avian influenza viruses.Lancet Microbe. 2022; 3: e804-e805Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar,5Carnaccini S Perez DR H9 influenza viruses: an emerging challenge.Cold Spring Harb Perspect Med. 2020; 10: a038588Crossref PubMed Scopus (46) Google Scholar Consequently, we strongly recommend immediate and meticulous surveillance, including regular or random sampling and testing, genomic monitoring in both animal and human populations, and heightened public awareness through widespread publicity, emphasising utmost urgency. We declare no competing interests. KL and XQ contributed equally. The study was funded by the National Key Research and Development Project of China (2021YFD1800202), the National Natural Science Foundation of China (32302958), and the Youth Program of the Natural Science Foundation of Jiangsu Province (BK20230575). KL, XW, and CB established the methodology and curated and investigated the data. KL and XQ visualised the data and performed the software analyses. KL and XQ wrote the original draft and reviewed and edited the manuscript. XW, CB, and XL supervised the study. XW, KL, and XL acquired funding. XW, CB, and KL managed the project. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Download .pdf (3.33 MB) Help with pdf files Supplementary appendix