Characterization of conserved properties of hemagglutinin of H5N1 and human influenza viruses: possible consequences for therapy and infection control

Presented results revealed that HA proteins encode highly conserved information that differ between influenza virus subtypes H5N1, H1N1, H3N2, H7N7 and defined an HA domain which may modulate interaction with receptor. We also found that about one third of H5N1 viruses which are isolated during the 2006/07 influenza outbreak in Egypt possibly evolve towards receptor usage similar to that of seasonal H1N1.The presented results may help to better understand the interaction of influenza virus with its receptor(s) and to identify new therapeutic targets for drug development.Influenza is currently considered as one of the most severe threats to human health and animal welfare. The highly pathogenic avian influenza (HPAIV) H5N1 viruses have been isolated from avian species in more than 50 countries. As of January 2008, 349 human H5N1 infections have been reported to the World Health Organization (WHO) [1]. Of these 349 cases, 216 patients have died (62%) and there has been no decline in mortality rate. Because the virus has evolving antigenicity for which humans may not have a pre-existing immunity, the conditions for a possible pandemic exist.The entry of influenza virus into susceptible cells is mediated by the viral hemagglutinin (HA) membrane glycoprotein which binds sialic acids of cell-surface glycoproteins and glycolipids. The binding preference of a given HA for different receptors correlates to some extent with the species specificity for infection. Human isolates preferentially bind to receptors with α2,6 linkages to galactose (SAα2,6Gal), whereas avian isolates prefer α2,3 linkages (SAα2,3Gal) [2-6]. A change in receptor preference is, however not necessary since the lower respiratory tract also expresses α 2.3 receptors [7]. It has also been reported that influenza virus can infect host cells via a sialic acid-independent pathway, either directly or in a multistage process [8]. It has been speculated that sialic acid enhances virus binding to secondary recepto