Globally, the researchers have been paying attention to the highly pathogenic avian influenza (HPAI) since the first human death caused directly by avian H5N1 virus in 1997. It is generally considered that the HPAI viruses were characterized by polybasic residues in the HA0 cleavage site in HA and the deletion of the stalk domain in NA [64] . However, these characteristics had been reported even before 1990s. The earliest H5N1 virus, ''A/ chicken/Scotland/1959 (H5N1)'', had four continuous basic residues in the HA0 cleavage site (compared to 5,6 continuous basic residues in most common H5N1 HAs); the stalked deletion of NA also existed in A/turkey/Ontario/84/1983 (H5N1). The records of H5N1 virus have increased rapidly since 2003. Since then, a number of new clades and subclades have emerged and resulted in various new glycosites ( Figure 3A and 3B) . The percentage of unconserved glycosites in HA also increased and diversified rapidly after 2003, meanwhile the percentage of unconserved glycosites in NA reduced gradually, regardless of those highly-conserved glycosites ( Figure 3C and 3D) .