Open AccessIdentification of Host Genes Linked with the Survivability of Chickens Infected with Recombinant Viruses Possessing H5N1 Surface Antigens from a Highly Pathogenic Avian Influenza Virus
Author(s) -
Yuko Uchida,
Chiaki Watanabe,
Nobuhiro Takemae,
Tsuyoshi Hayashi,
Takehiko Oka,
Toshihiro Ito,
Takehiko Saito
Publication year - 2012
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.06374-11
Subject(s) - biology , virology , influenza a virus subtype h5n1 , gene , neuraminidase , virus , recombinant dna , hemagglutinin (influenza) , host (biology) , microbiology and biotechnology , genetics
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 bothin vitro andin 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 ,AC3HAV1 ,PLA2G6 ,GCH1 , andUSP18 , 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.