H9N2 avian influenza viruses sporadically infect humans worldwide. These viruses have also contributed internal genes to H5N1, H5N6, H7N9, and H10N8 viruses, which have been isolated from humans with infections and are a substantial public health threat. To investigate the potential pathogenic mechanism of the H9N2 virus, we performed serial lung-to-lung passage of an avirulent H9N2 avian influenza virus (A/Chicken/Shandong/416/2016 [SD/416]) in mice to increase the pathogenicity of this virus. We generated a mouse-adapted (MA) virus that exhibited increased viral titers in the lungs, caused severe lung damage in mice, and induced body weight loss in mice; however, the avirulent parental virus did not cause any clinical symptoms in infected mice. Global gene expression analysis was performed and indicated that the transcriptional responses of these viruses were distinct. The lungs of mice infected with the MA virus exhibited the downregulation of genes related to innate immunity and ubiquitin-mediated proteolysis, which was not seen in infections with the avirulent parental virus. These data indicated that the MA virus might evade immune surveillance and changed its replication capacity to increase the viral replication level and pathogenicity. Our study demonstrates that host factors play an important role in the adaptive evolution of influenza virus in new hosts.

中文翻译：

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小鼠对H9N2禽流感病毒的适应导致小鼠与先天免疫应答和泛素介导的蛋白水解有关的基因下调。

H9N2禽流感病毒偶发感染全世界的人类。这些病毒还为H5N1，H5N6，H7N9和H10N8病毒贡献了内部基因，这些基因已从感染人类的​​病毒中分离出来，对公共健康构成重大威胁。为了研究H9N2病毒的潜在致病机制，我们在小鼠中进行了无毒H9N2禽流感病毒（A / Chicken / Shandong / 416/2016 [SD / 416]）的肺对肺连续传代，以增加H9N2病毒的致病性。该病毒。我们产生了一种适应小鼠的（MA）病毒，该病毒在肺部表现出更高的病毒滴度，对小鼠造成了严重的肺损伤，并在小鼠中引起了体重减轻。但是，无毒的亲本病毒不会在感染的小鼠中引起任何临床症状。进行了全局基因表达分析，并表明这些病毒的转录反应是不同的。被MA病毒感染的小鼠的肺部表现出与先天免疫和泛素介导的蛋白水解相关的基因的下调，这在无毒的亲本病毒的感染中没有发现。这些数据表明MA病毒可能逃避免疫监视并改变其复制能力以增加病毒复制水平和致病性。我们的研究表明，宿主因素在新宿主中流感病毒的适应性进化中起重要作用。在无毒的亲本病毒感染中未见到。这些数据表明MA病毒可能逃避免疫监视并改变其复制能力以增加病毒复制水平和致病性。我们的研究表明，宿主因素在新宿主中流感病毒的适应性进化中起着重要作用。在无毒的亲本病毒感染中没有发现。这些数据表明MA病毒可能逃避免疫监视并改变其复制能力以增加病毒复制水平和致病性。我们的研究表明，宿主因素在新宿主中流感病毒的适应性进化中起重要作用。