Avian influenza viruses (AIVs) are a persistent global threat, causing significant public health and agricultural concerns due to their potential for cross-species transmission. The emergence of the H6N1 avian influenza virus as a human pathogen has highlighted the evolving risk of these viruses spreading to mammals. A recent study investigates the progressive adaptation of Taiwan’s H6N1 lineage, tracking its increased ability to infect and transmit among mammals.
Progressive Adaptation to Mammalian Hosts
The study focused on comparing three temporally distinct H6N1 strains:
- A/Chicken/Taiwan/CF19/2009 (Ck/09)
- A/Chicken/Taiwan/2267/2012 (Ck/12)
- human isolate A/Taiwan/02/2013 (Hu/13)
Researchers found a significant increase in the replication efficiency of these strains in mammalian cells, with Hu/13 showing the most pronounced ability to replicate in MDCK cells (canine kidney cells), as evidenced by larger plaque sizes and higher viral titers compared to the avian isolates.
In mammals, Hu/13demonstrated heightened pathogenicity, causing severe disease and high mortality in mice, whereas earlier isolates like Ck/09 exhibited minimal morbidity.
Increased Transmissibility in Ferrets
Ferrets, a common mammalian model for studying influenza transmission, were used to assess the virus’s ability to spread between individuals. Hu/13 was highly transmissible, infecting all direct-contact ferrets and even one airborne-contact ferret. In contrast, the earlier isolates, Ck/09 and Ck/12, showed limited or no transmissibility, underscoring the growing risk of Hu/13 spreading in human populations under the right conditions.
Pathological Changes and Immune Responses
Ferrets infected with Hu/13 displayed severe lung pathology, including bronchial necrosis and extensive inflammatory cell infiltration. This contrasted with the mild pathology observed in Ck/09 infections. The study also examined the immune response in infected ferrets, noting elevated levels of proinflammatory cytokines in animals infected with Hu/13 which correlated with its increased virulence.
Molecular Mutations Enhancing Adaptation
Next-generation sequencing of Hu/13 revealed mutations in several key viral proteins, including PB1, HA (hemagglutinin), and NP (nucleoprotein), that are believed to enhance its ability to replicate and transmit in mammals. Interestingly, Hu/13 did not show canonical mammalian-adaptive mutations such as PB2-E627K or HA-Q226L, suggesting that the virus can adapt to mammals through alternate mutations that enhance its mammalian tropism.
Implications for Zoonotic Risk and Surveillance
The study highlights the progressive zoonotic potential of Taiwan’s H6N1 lineage, emphasizing the need for enhanced surveillance and monitoring. As these viruses continue to evolve in domestic poultry populations, there is an increasing risk of further adaptation, enabling them to infect humans and other mammals more efficiently.
Implications for Public Health and Pandemic Preparedness
The study underscores the importance of monitoring avian influenza viruses in both poultry and wild birds. Early detection of mutations that enhance mammalian adaptation can help mitigate the risk of future zoonotic outbreaks.
While some canonical mutations have been well-documented in other influenza strains, Hu/13 did not require these typical changes to transmit efficiently in ferrets. This finding suggests that other, less-characterized mutations may be contributing to its mammalian adaptation. Continued research into these mutations could provide valuable insights into influenza evolution.
One-Health Approach
The findings emphasize the need for a One-Health approach, which recognizes the interconnectedness of human, animal, and environmental health. Monitoring avian populations in high-risk regions like Taiwan, where domestic poultry production is extensive, is critical in preventing the spillover of influenza viruses to humans.
Disclaimer: The study referenced in this article is a preprint and has not yet been peer-reviewed.
Zheng, Z.; Chen, X.; Zheng, R.; Yan, Z.; Li, L.; Chen, R.; Li, L.; Liu, Y.; Guan, Y.; Zhu, H. Progressive Adaptation of H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity and Transmissibility. Preprints 22 April 2025.