

Most AI viruses are of low pathogenicity and cause asymptomatic or mild infection in avian species, but some strains of H5 and H7 are highly pathogenic. In contrast, human viruses prefer epithelial cells containing α 2,6 galactose linked-sialic acid ( α 2,6 gal-SA). Avian viruses prefer epithelial cell receptors containing α2,3-galactose linked-sialic acid ( α2,3 gal-SA). The receptor preference for avian influenza (AI) viruses and human influenza viruses is different. The subtypes that infect humans comprise H1N1, H2N2 (already extinct), and H3N2 viruses. Viruses of various HA and NA combinations, i.e., between H1-H16 and N1-N9, are found in avian species, while H17N10 and H18N11 are batlike viruses. Presently, the influenza A virus consists of 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes. However, a mutation changes near the receptor binding domain may play an important role in determining the cell tropism and is needed to be further explored. Our study suggested that the adaptation changes for the viral fitness to survive in a new host species (MDCK cells) might involve many genes, for example, the amino acid substitution 177G or 177W adjacent to the receptor-binding residues in the HA1 globular head and the substitution M315I in PB2. The changes were more commonly observed in the lung, particularly in the HA and NA genes. However, there was no change in the amino acid residues that determined the viral virulence. The virus isolates from the trachea, lung, and fecal specimens showed 27 nucleotide substitutions, leading to the changes of 18 amino acid residues. These sequences were compared to those derived from the virus isolates grown in Madin Darby canine kidney (MDCK) cells. The sequencing data from the autopsy specimens revealed at least 8 quasispecies of the H5N1 viruses across all 4 specimen types. Phylogenetic analysis of the viral genomes showed that these viruses belonged to clade 1 and were the reassortants generated from the reassortment of the viruses within the same clade. The entire H5N1 highly pathogenic avian influenza viral genomes were identified in the frozen autopsy specimens: the trachea, lung, colon, and intestinal feces from a patient who died of the disease in 2006.
