A research team at the University of Hong Kong’s LKS School of Medicine (HKUMed) has developed a machine learning classifier that can analyze the genome of influenza A virus (IAV) to accurately predict the potential risk of transmission among mammals.
A research team has successfully identified an important clue that explains the interspecies transmission of influenza A viruses from birds to mammals and then to humans. The study found that a decrease in guanine (G) or cytosine (C) associated with the IVA genome increases the risk of the virus persistently infecting mammals, including humans. The research team recommends incorporating this genomic signature into future influenza pandemic risk assessment frameworks to facilitate early identification of high-risk virus strains.
There are many different types of influenza viruses, including IAV (also known as avian influenza), which is common in birds and can infect other animals, including mammals and humans. If avian influenza viruses successfully adapt to the mammalian host environment and, more importantly, acquire the ability to transmit from human to human, they could cause an influenza pandemic and pose a serious threat to public health.
Distinguishing high-risk viruses using genomic signatures
A research team led by Associate Professor Tommy Lam Tsang-yuk from the School of Public Health at the University of Hong Kong analyzed a large IAV genetic dataset to compare characteristics across different virus lineages. Based on these genomic features, researchers classified IAV into two major groups. One group is primarily transmitted among birds and only occasionally infects mammals. while the other is capable of persistent transmission between mammalian hosts.
This study further revealed that among the virus lineages that can persist and circulate among mammals, the earliest viruses have reduced GC-associated content. This indicates that genomic features play an important role in interspecific adaptation processes and may facilitate the ability of IAV to maintain infection in mammals.
Recently, H5 virus strains, especially the highly pathogenic clade 2.3.4.4b, have received widespread attention, and reduced GC-associated content has also been demonstrated in cases involving mink, fox, and human infections. The research team believes this lineage has a high potential risk of evolving into a human influenza virus. Therefore, we recommend adding GC-related content to pandemic risk assessment tools and implementing stricter monitoring and precautionary measures.
AI-powered influenza surveillance strengthens public health preparedness
Based on their findings, the research team developed a machine learning classifier that accurately predicts the potential risk of persistent infection in mammals based on the genomic content of influenza viruses (https://iav-transmission.org/).
Professor Tommy Lamb pointed out that since 2021 there has been a marked increase in sporadic infections in humans and other mammals with highly pathogenic avian influenza H5 viruses of avian origin. Many of these cases are associated with viruses of clade 2.3.4.4b, which have recently been reported in dairy cattle. “It remains unclear which of the many IAVs that primarily circulate in birds are able to adapt and maintain infection in mammals,” he said. This represents a serious public health problem. ”
Professor Lam emphasized that the introduction of more sophisticated risk assessment methods, including the incorporation of GC-related genomic content, will help strengthen surveillance efforts, facilitate early detection of high-risk viruses, and enable timely action at the early stages of human infection.
reference: Ye Y, Shuai H, Song Y et al. Genomic features associated with persistent mammalian infection of avian influenza A viruses. natural microorganisms. 2026;11(3):802-814. doi: 10.1038/s41564-025-02257-4
This article has been reprinted from the following material: Note: Materials may be edited for length and content. Please contact the citation source for details. You can access our press release publishing policy here.
