Phylogeography of Avian influenza A H9N2 in China

Background: During the past two decades, avian influenza A H9N2 viruses have spread geographically and ecologically in China. Other than its current role in causing outbreaks in poultry and sporadic human infections by direct transmission, H9N2 virus could also serve as an progenitor for novel human avian influenza viruses including H5N1, H7N9 and H10N8. Hence, H9N2 virus is becoming a notable threat to public health. However, despite multiple lineages and genotypes that were detected by previous studies, the migration dynamics of the H9N2 virus in China is unclear. Increasing such knowledge would help us better prevent and control H9N2 as well as other future potentially threatening viruses from spreading across China. The objectives of this study were to determine the source, migration patterns, and the demography history of avian influenza A H9N2 virus that circulated in China. Results: Using Bayesian phylogeography framework, we showed that the H9N2 virus in mainland China may have originated from the Hong Kong Special Administrative Region (SAR). Southern China, most likely the Guangdong province acts as the primary epicentre for multiple H9N2 strains spreading across the whole country, and eastern China, most likely the Jiangsu province, acts as an important secondary source to seed outbreaks. Our demography inference suggests that during the long-term migration process, H9N2 evolved into multiple diverse lineages and then experienced a selective sweep, which reduced its genetic diversity. Importantly, such a selective sweep may pose a greater threat to public health because novel strains confer higher fitness advantages than strains being replaced and could generate new viruses through reassortment. Conclusion: Our analyses indicate that migratory birds, poultry trade and transportation have all contributed to the spreading of the H9N2 virus in China. The ongoing migration and evolution of H9N2, which poses a constant threat to the human population, highlights the need for a more comprehensive surveillance of wild birds and for the enhancement of biosafety for China's poultry industry.