National Institute of Animal Health (NIAH)

Topics in Animal Health Research 2011

20. Increased pathogenicity of avian influenza viruses related to amino acid mutation in polymerase-related viral proteins


 The molecular basis of the pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in chickens remains largely unknown. Despite the high amino acid homology (98%) between H5N1 A/chicken/Yamaguchi/7/2004 virus (CkYM7) and H5N1 A/duck/Yokohama/aq10/2003 virus (DkYK10), the former replicates rapidly in the macrophages and vascular endothelial cells in chickens and causes sudden death without fever or gross lesions, whereas the latter induces high fever, severe gross lesions, and a prolonged time to death. To explore the molecular basis of this difference in pathogenicity, we compared a series of 8 single-gene reassortant viruses from these HPAI viruses for pathogenicity in chickens. Two reassortants with the NP or PB2 gene of CkYM7 were shown to increase pathogenicity. The valine at position 105 in NP is responsible for this phenomenon. To explore the genetic basis of adaptation of duck-origin virus to chickens, we passaged DkYK10 5 times in the brains of chickens. The brain-passaged DkYK10-B5 quickly killed the chickens through rapid and efficient replication in tissues and severe apoptosis. The threonine at position 109 in NP contributed to increased viral replication and polymerase activity in chicken embryo fibroblasts. These results demonstrate that the amino acid mutations in NP enhance both viral RNA synthesis and the pathogenicity of HPAI viruses in chickens.
(Viral Disease and Epidemiology Research Division)


  • Tada T. et al (2011) J. Virol. 85:1834-1846
  • Tada T. et al (2011) J. Virol. 85:10354-10363