Table_1_Transcriptome Profiles of Highly Pathogenic Pure Avian H7N9 Virus-Infected Lungs of BALB/c Mice.DOCX

Avian influenza A (H7N9) viruses emerged in China in 2013 and caused a zoonotic disease associated with a high case-fatality ratio of more than 30%. Transcriptional profiles obtained using animal models reveal host responses to the disease, thereby providing insights into disease pathogenesis. Therefore, we aimed to characterize the host responses of the H7N9 virus infected-mouse lungs in this study. First, we isolated an avian-originated H7N9 strain, which was shown to be highly pathogenic to both chickens and mice. Genomic analysis results suggested that a 12-nucleotide-insertion was present at the hemagglutinin cleavage site, and both the hemagglutinin and neuraminidase genes belonged to the Yangtze River Delta lineage. RNA sequencing results revealed 566 differentially expressed genes in the H7N9-infected lungs. Moreover, transcriptome analysis revealed that over-activated antiviral signals and intense interferon-stimulated gene products possibly contributed to the high virulence of the virus in mice. Importantly, lung concentrations of inflammatory cytokines, including interleukin-1β and interleukin-6, interferon-β, and tumor necrosis factor-α, were upregulated in response to H7N9 virus infection. Overall, the present study provided a comprehensive understanding of H7N9 virus pathogenicity and correlated host immune responses.H7N9亚型甲型禽流感病毒（Avian influenza A (H7N9)）于2013年在中国首次出现，引发了一种病死率超过30%的人畜共患病。利用动物模型获取的转录组谱能够揭示宿主对该疾病的应答特征，进而为疾病发病机制的研究提供全新视角。因此，本研究旨在解析H7N9病毒感染小鼠肺部的宿主应答特征。本研究首先分离得到一株禽源H7N9毒株，该毒株对鸡和小鼠均具有高致病性。基因组分析结果显示，该毒株的血凝素（hemagglutinin）裂解位点存在12个核苷酸插入序列，且血凝素与神经氨酸酶（neuraminidase）基因均属于长江三角洲谱系。RNA测序（RNA sequencing）结果显示，H7N9病毒感染的肺部组织中存在566个差异表达基因。此外，转录组分析结果显示，过度激活的抗病毒信号与大量干扰素刺激基因产物，可能是该病毒对小鼠具有高毒力的重要诱因。值得注意的是，感染H7N9病毒后，肺部炎症细胞因子（包括白细胞介素-1β（interleukin-1β）、白细胞介素-6（interleukin-6）、干扰素β（interferon-β）以及肿瘤坏死因子α（tumor necrosis factor-α））的浓度均出现显著上调。综上，本研究全面阐明了H7N9病毒的致病机制及其与宿主免疫应答的关联。