Assessment of the public health risk of novel reassortant H3N3 avian influenza viruses that emerged in chickens

Influenza A (H3N2) viruses are historically responsible for the 1968 Hong Kong flu pandemic. Since then, H3N2 has continued to circulate as a seasonal influenza virus in humans. Public health concerns were raised in 2022 when human infections with novel reassortant H3N8 influenza viruses originating from chickens were first reported in China. Here, we conducted a systematic surveillance of H3 avian influenza viruses (AIVs) circulating in poultry and assessed the public health risk of emergent H3 reassortants. We found that H3 AIVs were prevalent in both ducks and chickens. Notably, in December 2022, a novel chicken-derived H3N3 subtype virus was identified, which gradually replaced the previously predominant H3N8 virus and became prevalent in chickens. Genetic analysis demonstrated that the novel H3N3 virus is a triple-reassortment strain with the H3 gene segment from chicken H3N8 virus, the N3 gene segment from the H10N3 virus, and internal gene segments derived from H9N2 viruses. Compared with chicken H3N8 and duck H3N3 viruses, the novel chicken H3N3 viruses produced higher yields and induced greater pathogenicity in human respiratory epithelial cells and mammalian models (mouse and ferret). Importantly, the chicken H3N3 viruses could be transmitted efficiently between ferrets through direct contact. The polymerase activity of the chicken H3N3 viruses in mammalian cells was markedly increased by the PA gene originating from the H9N2 virus. Our findings indicate that the circulation of novel chicken H3N3 viruses poses a threat to both the poultry industry and human public health.IMPORTANCEThe H3Ny subtype influenza A virus can infect a wide range of hosts. In addition to circulating among wild birds and poultry, the virus can also infect humans and a variety of mammals. Here, we found that H3Ny subtype AIVs were widely prevalent in domestic chickens and ducks. Novel H3N3 reassortant viruses emerged as a result of the genetic reassortment of the chicken-derived H3N8 AIVs with H10N3 and H9N2 AIVs. The novel H3N3 subtype AIVs are gradually displacing H3N8 AIVs and becoming prevalent in chickens. Furthermore, these novel H3N3 AIVs exhibited enhanced infection ability and efficient transmissibility in mammalian models, indicating a growing potential public health risk.