title: Identification of host genes linked with the survivability of chickens infected with recombinant viruses possessing H5N1 surface antigens from a highly pathogenic avian influenza virus.
abstract: Seventeen recombinant viruses were generated by a reverse genetic technique to elucidate the pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) in chickens. The recombinant viruses generated possessed hemagglutinin (HA) and neuraminidase (NA) genes from an HPAIV. Other segments were combinations of the genes from an HPAIV and two low-pathogenic avian influenza viruses (LPAIVs) derived from chicken (LP) and wild bird (WB). Exchange of whole internal genes from an HPAIV with those of an LPAIV resulted in a significant extension of the survival time following intranasal infection of the chickens with the recombinants. Survival analysis demonstrated that the exchange of a gene segment affected survivability of the chickens with statistical significance. The analysis revealed three groups of recombinants with various gene constellations that depended upon the survivability of the infected chickens. Recombinants where the PA gene was exchanged from LP to WB in the LP gene background, LP (W/PA), did not kill any chickens. LP (W/PA) replicated less efficiently both in vitro and in vivo, suggesting that the intrinsic replication ability of LP (W/PA) affects pathogenicity; however, such a correlation was not seen for the other recombinants. Microarray analysis of the infected chicken lungs indicated that the expression of 7 genes, CD274, RNF19B, OASL, ZC3HAV1 [corrected] , PLA2G6, GCH1, and USP18, correlated with the survivability of the chickens infected (P < 0.01). Further analysis of the functions of these genes in chickens would aid in the understanding of host gene responses following fatal infections by HPAIVs.
authors.affiliation: Viral Disease and Epidemiology Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), Ibaraki, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Uchida
authors.forename: Chiaki
authors.initials: C
authors.lastname: Watanabe
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takemae
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Oka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.forename: Takehiko
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D005585:Influenza in Birds / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000821:virology; D008168:Lung / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase