title: Rapid death of duck cells infected with influenza: a potential mechanism for host resistance to H5N1.
abstract: Aquatic birds are the natural reservoir for most subtypes of influenza A, and a source of novel viruses with the potential to cause human pandemics, fatal zoonotic disease or devastating epizootics in poultry. It is well recognised that waterfowl typically show few clinical signs following influenza A infection, in contrast, terrestrial poultry such as chickens may develop severe disease with rapid death following infection with highly pathogenic avian influenza. This study examined the cellular response to influenza infection in primary cells derived from resistant (duck) and susceptible (chicken) avian hosts. Paradoxically, we observed that duck cells underwent rapid cell death following infection with low pathogenic avian H2N3, classical swine H1N1 and 'classical' highly pathogenic H5N1 viruses. Dying cells showed morphological features of apoptosis, increased DNA fragmentation and activation of caspase 3/7. Following infection of chicken cells, cell death occurred less rapidly, accompanied by reduced DNA fragmentation and caspase activation. Duck cells produced similar levels of viral RNA but less infectious virus, in comparison with chicken cells. Such rapid cell death was not observed in duck cells infected with a contemporary Eurasian lineage H5N1 fatal to ducks. The induction of rapid death in duck cells may be part of a mechanism of host resistance to influenza A, with the loss of this response leading to increased susceptibility to emergent strains of H5N1. These studies provide novel insights that should help resolve the long-standing enigma of host-pathogen relationships for highly pathogenic and zoonotic avian influenza.
authors.affiliation: Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Suresh V
authors.initials: SV
authors.lastname: Kuchipudi
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Dunham
authors.forename: Rahul
authors.initials: R
authors.lastname: Nelli
authors.forename: Gavin A
authors.initials: GA
authors.lastname: White
authors.forename: Vivien J
authors.initials: VJ
authors.lastname: Coward
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Slomka
authors.forename: Ian H
authors.initials: IH
authors.lastname: Brown
authors.forename: Kin Chow
authors.initials: KC
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002645:Chickens; D053938:DNA Fragmentation; D004372:Ducks; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000502:physiology*; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D061251:Primary Cell Culture; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013552:Swine; D013997:Time Factors
chemical_list: D012367:RNA, Viral; D011956:Receptors, Cell Surface; C092488:sialic acid receptor; D053148:Caspase 3; D053179:Caspase 7