03 Nov 2025

H9N2: An overlooked AI strain that might be the next pandemic risk

“H9N2 might be more prevalent than we realize,” said Michelle Wille of the Peter Doherty Institute for Infection and Immunity.

aviNews Asia

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Experiments suggests low pathogenic avian influenza (AI) H9N2 has adapted to human cells, but cases of person-to-person transmission have not been reported yet.

An AI virus that has often been ignored because it mostly causes minor disease in birds has the potential to cause a human pandemic, said a team that has tracked how the H9N2 virus has become better adapted to infect people.

The researchers said more surveillance of the virus is needed.

In the past few years, surveillance has been focused on the AI virus H5N1, which has spread across most continents and can cause severe disease and death in people. Since 2020, H5N1 has killed about 21 people. In North America, the virus is also spreading among dairy cows.

Less attention is being paid to H9N2, said Kelvin To, a clinical microbiologist at the University of Hong Kong, despite the virus being the second most common strain of AI that infects people.

H9N2 has caused 173 infections in people since 1998, mostly in China, said Dr To, who presented his team’s research at the Pandemic Research Alliance International Symposium in Melbourne, Australia, recently.

“H9N2 might be more prevalent than we realize,” said Michelle Wille, who studies AI at the Peter Doherty Institute for Infection and Immunity in Melbourne.

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Infections are probably being missed because they do not result in severe infection or hospitalization in people, or because people are more commonly tested for the H5N1 instead, she added.

Genetic changes

Scientists are yet to find evidence of person-to-person transmission of H9N2, which would be needed for it to lead to a pandemic. But Dr To and his team have found that H9N2 underwent genetic changes that began around 2015 that have made the virus more infectious.

In cell-based experiments, a version of the H9N2 virus collected in 2024 infected more human cells than did a historical sample collected in 1999. The modern version also showed improved binding to various receptors on human cells. This means the virus has adapted to spread among people, reported Dr To and his colleagues in Emerging Microbes & Infections recently.

The virus would have to undergo several more changes before it could cause sustained transmission between people, said Dr Wille.

The virus must change to preferentially bind to human receptors instead of receptors found in bird cells and must adapt how well it grows at temperatures and pH levels of humans, which are different from birds.

Increased surveillance and communication about the risks of AI is needed, said Dr Wille. Part of the issue is that countries are not required to report infections caused by strains that are considered to be of low pathogenicity, such as H9N2.

Dr To said greater virus surveillance among mammals in close contact with wild birds or poultry would help scientists understand whether the virus has been adapted to mammals other than humans.

He is concerned that when animals are infected with multiple viruses, genetic material gets mixed and matched when the viruses replicate inside the cell and could create new viruses that can infect humans.

Scientists are concerned that this reassortment could also happen in people, too. Dr To said other research has found genetic material from H9N2 among the viruses that have caused previous AI outbreaks in people.

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