New Study Details H9N2 Avian Flu’s Variability and Public Health Implications

A study published in Nature Microbiology has identified extensive genetic and antigenic variation among H9N2 avian influenza viruses (AIVs) circulating in poultry across China. The findings highlight the potential public health risks associated with these viruses.

H9N2, first detected in China in 1994, has remained the dominant strain in poultry despite ongoing vaccination efforts. Its continued presence, along with an increase in reported human infections, has raised public health concerns.

The mechanisms behind the virus’s ability to infect humans and transmit between species were not well understood. To address this, a team led by Professor Yuhai Bi and George F. Gao from the Chinese Academy of Sciences’ Institute of Microbiology, along with Professor Weifeng Shi from Ruijin Hospital at Shanghai Jiao Tong University School of Medicine, studied the virus’s genetic changes, antigenic diversity, and adaptive mutations.

Their research offers new insight into how H9N2 adapts to mammals and avoids the human MxA gene-mediated immune response.

Since 2014, Professor Bi and teams from the Center for Influenza Research and Early-warning (CASCIRE) have monitored cross-species transmission and carried out surveillance of AIVs in China. Data collected in live poultry markets between 2019 and 2023 showed that viruses from the A/chicken/Beijing/1/94 (BJ94) lineage have remained dominant.

To better understand how these viruses are evolving, the researchers developed a new clade classification method for BJ94 strains based on genetic distance and phylogenetic analysis. They also launched an online tool to help researchers track and study H9 AIV evolution.

Using this framework, they identified eleven hemagglutinin (HA) sub-subclades currently co-circulating in poultry, each with distinct antigenic features. These differences may explain why existing vaccines have been unable to fully control the spread of H9N2.

The study also found that mutations linked to increased infectivity and pathogenicity in mammals are becoming more common. For example, the HA-L226 mutation, which promotes binding to human receptors, appeared in 99.46 % of isolates collected between 2021 and 2023. The NP-N52 mutation, associated with resistance to the human MxA protein, and the PB2-V627 mutation, known to enhance viral replication in human cells, were also frequently detected.

Laboratory tests showed that strains with these mutations could replicate in human cells, bind more readily to human-type receptors, and transmit via aerosols and direct contact in ferrets and guinea pigs. These traits are considered indicators of zoonotic potential.

The findings suggest that H9N2 AIVs pose an increasing risk of transmission to humans. The study underscores the need for enhanced surveillance, updated vaccination strategies, and a deeper understanding of the virus’s evolution to address the ongoing public health threat.