Amino Acid Residues 253 and 591 of the PB2 Protein of Avian Influenza Virus A H9N2 Contribute to Mammalian Pathogenesis

被引:67
作者
Mok, Chris Ka Pun [1 ]
Yen, Hui Ling [1 ]
Yu, May Yan Mei [1 ]
Yuen, Kit Man [1 ]
Sia, Sin Fun [1 ]
Chan, Michael Chi Wai [1 ]
Qin, Gang [2 ]
Tu, Wen Wei [2 ]
Peiris, Joseph Sriyal Malik [1 ]
机构
[1] Univ Hong Kong, Queen Mary Hosp, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Pediat & Adolescent Med, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China
关键词
BRONCHIAL EPITHELIAL-CELLS; A H5N1 VIRUSES; HONG-KONG; HUMAN INFECTION; REPLICATION; POLYMERASE; RESPONSES; TROPISM; MICE;
D O I
10.1128/JVI.00702-11
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-alpha) 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.
引用
收藏
页码:9641 / 9645
页数:5
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