title: Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif.
abstract: The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio-economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host-pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population.
authors.affiliation: Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Geelong, Victoria, Australia.|School of Medicine, Deakin University, Geelong, Victoria, Australia.
authors.forename: Jasmina M
authors.initials: JM
authors.lastname: Luczo
authors.affiliation: School of Medicine, Deakin University, Geelong, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Stambas
authors.affiliation: Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Geelong, Victoria, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Durr
authors.affiliation: Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Geelong, Victoria, Australia.
authors.forename: Wojtek P
authors.initials: WP
authors.lastname: Michalski
authors.affiliation: Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Geelong, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Bingham
mesh_terms: D000818:Animals; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000473:pathology* / Q000635:transmission / Q000821:virology*; D059748:Proteolysis; D037521:Virulence Factors / Q000378:metabolism*; D015047:Zoonoses / Q000473:pathology / Q000635:transmission / Q000821:virology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037521:Virulence Factors; C109963:hemagglutinin, avian influenza A virus