Since 2003, multiple highly pathogenic avian influenza A (HPAI) H5 subtypes, including H5N1, H5N2, H5N6, and H5N8, have generated severe epidemics and thus not only tremendous economic losses in the domestic poultry industry, but also serious threats to human health worldwide (Jhung and Nelson, 2015). As of October 3, 2016, at least 856 cases of human infection with avian influenza A (H5N1) virus in 16 countries had been reported to the World Health Organization, among which 452 had ended in death, for an apparent case fatality rate of 52.8% (WHO, 2016). As the natural reservoir for avian influenza viruses (AIVs), wild bird populations can be infected by many such viruses, including the H3, H5, and H7 subtypes AIVs, and thus play a critical role in AIV epidemiology and ecology (Claes et al., 2016; Dhingra et al., 2016; Kang et al., 2017). Thus far, results of the phylogenetic analysis of the hemagglutinin (HA) gene have revealed multiple clades and subclades of H5 subtype AIVs. Among them, H5N6 has replaced H5N1 as the dominant subtype in southern China (Bi et al., 2016a), while clade 2.3.4.4 of AIVs is now considered to be the dominant in China (Saito et al., 2015; Claes et al., 2016). Given recent suggestions that clade 2.3.4.4 of AIVs has become increasingly pathogenic to domestic poultry and wild birds (Claes et al., 2016; Sun et al., 2016), AIV virulence is likely affects multiple factors and depends upon both antigenic drift and the AIV-infected strain in the host immunity (Tscherne and Garcia-Sastre, 2011).