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

J Virol. 2011 Sep;85(18):9641-5. Epub 2011 Jul 6.

Mok CK, Yen HL, Yu MY, Yuen KM, Sia SF, Chan MC, Qin G, Tu WW, Peiris JS.

Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.

Abstract

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 minireplicon assays, induced more tumor necrosis factor alpha (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.