Amino acid residues 253 and 591 of the PB2 protein of avian influenza virus A H9N2 contributes to mammalian pathogenesis

Mok CK, Yen HL, Yu MY, Yuen KM, Sia SF, Chan MC, Q. Amino acid residues 253 and 591 of the PB2 protein of avian influenza virus A H9N2 contributes to mammalian pathogenesis. J Virol. 2011 Jul 6
submited by kickingbird at Jul, 13, 2011 10:39 AM from J Virol. 2011 Jul 6

We investigated the tropism, host responses and virulence of two variants of A/Quail/Hong Kong/G1/1997 (H9N2) (H9N2/G1) with D253N and Q591K in the PB2 protein in primary human macrophages and bronchial epithelium in vitro and in mice in vivo. Virus with PB2 D253N and Q591K had greater polymerase activity in mini-replicon assays, induced more TNF-α in human macrophages, replicated better in differentiated normal human bronchial epithelial (NHBE) cells and was more pathogenic for mice. Taken together, our studies help define the viral genetic determinants that contribute to pathogenicity of H9N2 viruses.