New genotypes of influenza A virus arise quickly and frequently around the world due to continued mutation and reassortment. Novel influenza A viruses pose a direct threat to immunologically naive humans. A prime example is the recent emergence of avian-origin H7N9 viruses that have become enzootic in China. Three waves of the H7N9 breakout that began in March 2013 have resulted in 571 human cases and over 212 deaths as of 23 February 2015. Real-time influenza surveillance at the wild bird– human interface is essential to limit the outbreak in scale and geographic distribution and to understand the pandemic potential of the H7N9 avian influenza. Influenza A viruses continue to evolve via several mechanisms, especially by point mutation and reassortment [1], which conduce to the emergence of new strains with epidemic or pandemic potential. In the last 100 years, influenza A viruses have transmitted to and spread among humans, resulting in at least four pandemics [2]. These outbreaks lead to huge economic losses. The recent outbreak of H7N9 viruses following the pandemic spread of 2009 pandemic influenza A(H1N1)pdm09 virus has caused more than 600 human infections, with nearly 30% mortality (http:// www.who.int/influenza/human_animal_interface/influenza_h7n9/en/). Multiple distinct lineages of H7N9 viruses have established in chickens [3]. Of note, the increasing epidemiological evidences indicated that H7N9 viruses have limited transmissibility in a family cluster [4]. Therefore, a comprehensive understanding of the mechanisms that determine viral transmissibility, pathogenicity, and evolution is of importance for pandemic preparedness.