Gong Wenxiao, Huang Kun, Zhang Yufei, He Xinglin, Li Chengfei, Mao Haiying, Wei Yanming, Zou Zhong, Jin Meilin
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Front Vet Sci. 2020 Dec 21;7:603584. doi: 10.3389/fvets.2020.603584. eCollection 2020.
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.
甲型禽流感（H7N9）病毒于2013年在中国出现，并引发了一种人畜共患病，病死率超过30%。利用动物模型获得的转录谱揭示了宿主对该疾病的反应，从而为疾病发病机制提供了见解。因此，在本研究中，我们旨在描述感染H7N9病毒的小鼠肺部的宿主反应。首先，我们分离出一株禽源H7N9毒株，该毒株对鸡和小鼠均具有高致病性。基因组分析结果表明，血凝素裂解位点存在一个12个核苷酸的插入，血凝素和神经氨酸酶基因均属于长江三角洲谱系。RNA测序结果显示，H7N9感染的肺部有566个差异表达基因。此外，转录组分析表明，过度激活的抗病毒信号和强烈的干扰素刺激基因产物可能导致该病毒在小鼠中的高毒力。重要的是，H7N9病毒感染后，包括白细胞介素-1β、白细胞介素-6、干扰素-β和肿瘤坏死因子-α在内的炎性细胞因子在肺部的浓度上调。总体而言，本研究全面了解了H7N9病毒的致病性及相关的宿主免疫反应。
