title: Suppression of avian influenza transmission in genetically modified chickens.
abstract: Infection of chickens with avian influenza virus poses a global threat to both poultry production and human health that is not adequately controlled by vaccination or by biosecurity measures. A novel alternative strategy is to develop chickens that are genetically resistant to infection. We generated transgenic chickens expressing a short-hairpin RNA designed to function as a decoy that inhibits and blocks influenza virus polymerase and hence interferes with virus propagation. Susceptibility to primary challenge with highly pathogenic avian influenza virus and onward transmission dynamics were determined. Although the transgenic birds succumbed to the initial experimental challenge, onward transmission to both transgenic and nontransgenic birds was prevented.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Lyall
authors.forename: Richard M
authors.initials: RM
authors.lastname: Irvine
authors.forename: Adrian
authors.initials: A
authors.lastname: Sherman
authors.forename: Trevelyan J
authors.initials: TJ
authors.lastname: McKinley
authors.forename: Alejandro
authors.initials: A
authors.lastname: Núñez
authors.forename: Auriol
authors.initials: A
authors.lastname: Purdie
authors.forename: Linzy
authors.initials: L
authors.lastname: Outtrim
authors.forename: Ian H
authors.initials: IH
authors.lastname: Brown
authors.forename: Genevieve
authors.initials: G
authors.lastname: Rolleston-Smith
authors.forename: Helen
authors.initials: H
authors.lastname: Sang
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiley
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D002645:Chickens / Q000235:genetics* / Q000821:virology; D002988:Cloaca / Q000821:virology; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology / Q000302:isolation & purification / Q000502:physiology*; D005585:Influenza in Birds / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D009960:Oropharynx / Q000821:virology; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral; D012324:RNA-Dependent RNA Polymerase