Of mice and men: the host response to influenza virus infection.
Of mice and men: the host response to influenza virus infection.
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DOI：
10.1007/s00335-018-9750-y
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Schughart K
中科院分区：
文献类型：
--
作者：
Kollmus H;Pilzner C;Leist SR;Heise M;Geffers R;Schughart K
流感病毒(IV)感染是一个非常严重的公共卫生问题。目前，还没有已建立的生物标志物来支持呼吸道病毒感染的诊断，更重要的是，支持严重的IV疾病的诊断。动物模型的研究对于了解导致严重IV疾病的生物、遗传和环境因素以及验证人类研究中的生物标记物候选是极其重要的。然而，由于动物研究主要集中在受感染的肺部，而在人类中，几乎所有的研究都使用患者的外周血液，这一事实往往会影响鼠与人之间的跨物种比较。此外，人类研究并不认为遗传背景是可变的，尽管人类群体在遗传上非常多样化。因此，在这项研究中，我们对IV感染后人类患者和高度遗传多样性的协作杂交(CC)小鼠群体的外周血液进行了跨物种的基因表达研究。我们的结果表明，在小鼠和人类中，单个基因表达的变化非常相似。在人类中受最高调控的基因在老鼠身上也有不同的调控。我们的结论是，小鼠是一个非常有价值的体内模型系统来验证和发现候选基因，这些候选基因可以用作人类的生物标志物。此外，小鼠研究允许在受控良好的实验系统中确认人类的发现，这为理解人类候选基因的表达和功能增加了巨大的价值。本文的在线版本(10.1007/s00335-0189750-y)包含补充材料，授权用户可以使用。
Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections and more importantly for severe IV disease. Studies in animal models are extremely important to understand the biological, genetic, and environmental factors that contribute to severe IV disease and to validate biomarker candidates from human studies. However, mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs, whereas in humans almost all studies use peripheral blood from patients. In addition, human studies do not consider genetic background as variable although human populations are genetically very diverse. Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. The top-regulated genes in humans were also differentially regulated in mice. We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. Furthermore, mouse studies allow confirmation of findings in humans in a well-controlled experimental system adding enormous value to the understanding of expression and function of human candidate genes. The online version of this article (10.1007/s00335-018-9750-y) contains supplementary material, which is available to authorized users.
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