The series of basic amino acids at the cleavage site of the hemagglutinin protein (HA) of the highly pathogenic avian influenza virus (HPAIV) is responsible for pathogenicity; however, the role of the internal gene products of HPAIVs in their pathogenicity has not been well established. To address this question, reverse genetics was utilized to generate artificial viruses with amino acid substitutions in the PB1 protein, one of the components of viral RNA polymerase, along with the HA from an HPAIV. A substitution at amino acid position 38 of the PB1 protein from cysteine to tyrosine (C38Y) enhanced viral polymerase activity by 5-fold. A valine-to-alanine substitution at position 14 (V14A) of the PB1 protein reduced the polymerase activity by 5-fold. An experimental infection study with the artificial viruses demonstrated that the C38Y substitution recovered the lethality of the virus and that the V14A substitution reduced the transmissibility of the virus in chickens. These results demonstrated that amino acid substitutions in the PB1 protein are involved in the pathogenicity of HPAIVs.
(Influenza and Prion Diseases Research Center)
References:
Suzuki Y. et al (2014) J. Virol. 88(19):11130-11139
