Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
J Virol. 2011 Sep;85(18):9641-5. doi: 10.1128/JVI.00702-11. Epub 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 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.
我们研究了两种 A/Quail/Hong Kong/G1/1997(H9N2)(H9N2/G1)变体在原代人巨噬细胞和体外支气管上皮细胞以及体内小鼠中的嗜性、宿主反应和毒力,这两种变体在 PB2 蛋白中有 D253N 和 Q591K 突变。具有 PB2 D253N 和 Q591K 的病毒在 minireplicon 测定中具有更高的聚合酶活性,在人巨噬细胞中诱导更多的肿瘤坏死因子α(TNF-α),在分化正常的人支气管上皮(NHBE)细胞中复制更好,对小鼠的致病性更强。综上所述,我们的研究有助于确定导致 H9N2 病毒致病性的病毒遗传决定因素。