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A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

机译:一种基于系统的方法来检查人和禽细胞中甲型流感病毒H7N9亚型感染期间的宿主反应

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摘要

Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.
机译:尽管甲型H7N9流感病毒在几种禽类中传播,但它也可以感染人类,并产生严重的疾病后果。为了更好地了解H7N9病毒的生物学特性,我们检查了宿主对禽类和人类细胞感染的反应。在这项研究中,我们使用了A / Anhui / 1/2013菌株,该菌株是在H7N9流行的第一波期间分离的。 H7N9病毒感染了人(气道上皮细胞)和禽类(小鸡胚成纤维细胞)细胞,并使用生物信息学工具检查了每个感染的宿主转录组,并将其与其他代表性的禽和人甲型流感病毒亚型进行了比较。 H7N9病毒在两种细胞系中诱导了更高的表达变化(差异调控基因),在禽类细胞中观察到了更显着的变化。差异表达基因的直系同源基因定位在H7N9感染期间鉴定出显着丰富的常见途径和细胞类型途径。该数据证实了我们先前的发现,即不同的A型流感病毒亚型在人和禽细胞中具有病毒特异性复制特征和抗病毒信号。此外,我们首次报道了禽细胞中新的HIPPO信号传导途径,我们认为它在维持H7N9病毒感染的禽细胞的抗病毒状态中起着至关重要的作用。这可以解释在检测出H7N9病毒呈阳性的禽类中没有疾病症状。

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