Influenza (flu) is a viral respiratory infection in mammals and birds. This virus is divided into three main types (A, B andC) . Influenza A is found in a wide variety of mammalian and avian species and is associated with the major humanpandemics. Influenza B is largely confined to humans and became unexpectedly prevalent in humans during 2000-2002. Influenza C infects humans, dogs and pigs and generally causes only mild upper respiratory tract infection. However, influenza A and B viruses cause a wide spectrum of severe disease including lower respiratory, tract infection, pneumonia and encephalitis. Influenza A is further divided into subtypes based on antigenic differences in themembrane proteins hemagglutinin (HA) and neuraminidase (NA) . 16 HAs (H1-H16) and 9 NA (N1-N9) had beenidentified. While different combinations of the two antigens appear more frequently in some groups of birds than others, only few subtypes have established themselves in humans (HA:H1, H2, and H3, NA: N1 and N2) . Sustained, widespread highly pathogenic avian influenza (HPAI) H5N1 epidemics represent a significant public healthhazard because they not only cause mortality in poultry but also increase the risk of a human influenza pandemic. In1997, the first case of human infected H5N1 was reported in Hongkong, China. Avian influenza have broken thespecies barrier and made heavy threaten to human health. In the process of epidemic, more than 100 countries hadfound more than 400 human avian influenza infected cases, within 262 patients dead. Since two human-to-humantransmission cases were reported in China, controlling the interspecies transmission of avian influenza is of criticalimportance. At least 4 major antigenic groups of H5N1 viruses currently in circulation have caused infection in humans. The recentemergence and development of the unique antigenic FJ-like virus (clade 2. 3. 4) in Asia, the continuous circulation andexpansion of Qinghai-like virus (clade 2. 2) in Europe, the Middle East, and Africa, and the persistent prevalence ofclade 2. 1 viruses in Indonesia, and classic Clade 1 in Vietnam and Hong Kong. Hemagglutinin (HA) , which binds to sialic acid (SA) -containing receptors on host cells, is the protein that producesneutralizing antibodies. Hemagglutinin plays a major role in the determination of host range restriction and virulencebecause human influenza HA preferentially binds to SA-α-2, 6 while avian influenza HA preferentially binds to SA-α-2, 3. The cleavage of HA into two disulfide-linked subunits, HA1 and HA2, is a prerequisite for initiating infection. Usually HAis restricted to be cleaved at respiratory tracts by limited proteases. Highly pathogenic avian influenza contains a stretchof basic residues adjacent to the HA cleavage site, enabling its HA to be cleaved by a wide range of proteases withubiquitous tissue distributions. This process permits productive virus replication in organs outside of the respiratory andgastrointestinal tracts, including the brain, resulting in widespread disease and high mortality rates.