As the number of human infections with avian and swine influenza viruses continues to rise, the pandemic risk posed by zoonotic influenza viruses cannot be underestimated. Implementation of global pandemic preparedness efforts has largely focused on H5 and H7 avian influenza viruses; however, the pandemic threat posed by other subtypes of avian influenza viruses, especially the H9 subtype, should not be overlooked. In this review, we summarize the literature pertaining to the emergence, prevalence and risk assessment of H9N2 viruses, and add new molecular analyses of key mammalian adaptation markers in the hemagglutinin and polymerase proteins. Available evidence has demonstrated that H9N2 viruses within the Eurasian lineage continue to evolve, leading to the emergence of viruses with an enhanced receptor binding preference for human-like receptors and heightened polymerase activity in mammalian cells. Furthermore, the increased prevalence of certain mammalian adaptation markers and the enhanced transmissibility of selected viruses in mammalian animal models add to the pandemic risk posed by this virus subtype. Continued surveillance of zoonotic H9N2 influenza viruses, inclusive of close genetic monitoring and phenotypic characterization in animal models, should be included in our pandemic preparedness efforts.
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