title: Amino acid residues 253 and 591 of the PB2 protein of avian influenza virus A H9N2 contribute to mammalian pathogenesis.
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.
authors: Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
authors: Chris Ka Pun
authors: CK
authors: Mok
authors: Hui Ling
authors: HL
authors: Yen
authors: May Yan Mei
authors: MY
authors: Yu
authors: Kit Man
authors: KM
authors: Yuen
authors: Sin Fun
authors: SF
authors: Sia
authors: Michael Chi Wai
authors: MC
authors: Chan
authors: Gang
authors: G
authors: Qin
authors: Wen Wei
authors: WW
authors: Tu
authors: Joseph Sriyal Malik
authors: JS
authors: Peiris
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D008264:Macrophages / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics* / Q000378:metabolism*; D012376:Rodent Diseases / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D056189:Viral Tropism; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000596:Amino Acids; C057027:PB2 protein, Influenzavirus A; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D037521:Virulence Factors; D012324:RNA-Dependent RNA Polymerase