iTRAQ-based quantitative proteomics reveals important host factors involved in the high pathogenicity of the H5N1 avian influenza virus in mice
iTRAQ-based quantitative proteomics reveals important host factors involved in the high pathogenicity of the H5N1 avian influenza virus in mice
复制标题
基于 iTRAQ 的定量蛋白质组学揭示了 H5N1 禽流感病毒对小鼠高致病性的重要宿主因素
DOI：
10.1007/s00430-016-0489-3
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发表时间：
2017-04-01
影响因子：
5.4
通讯作者：
Liu, Xiufan
中科院分区：
文献类型：
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作者：
Hu, Jiao;Gao, Zhao;Liu, Xiufan
我们以前曾报道过一对H5 N1禽流感病毒，它们在基因上相似，但在小鼠中的毒力差异很大。A/Chicken/Jiangsu/k 0402/2010（CK 10）对小鼠具有高致死性，而A/Goose/Jiangsu/k 0403/2010（GS 10）为无毒力。在这项研究中，调查的宿主因素，占其毒力的差异，我们比较了病理学和宿主蛋白质组的CK 10或GS10感染的小鼠肺。早在感染的第一天就从CK 10感染的动物中观察到中度肺损伤，并且在稍后的时间点病理学稳定地进展。然而，在感染晚期阶段，在GS 10感染的小鼠肺中仅观察到轻度病变。使用定量iTRAQ耦合LC-MS/MS方法，我们首次发现与CK 10相比，GS10刺激了更显著的差异表达（DE）蛋白。然而，DE蛋白的生物功能分析表明，CK 10诱导的炎症反应相关功能比GS 10强得多。经典途径分析还表明，CK 10高度激活“急性期反应信号”，这导致对病毒感染的广泛生物活性，包括许多炎症过程。进一步的深入分析表明，CK 10加剧了急性肺损伤相关反应，包括炎症反应、细胞死亡、活性氧产生和补体反应。此外，这些鉴定的与肺损伤相关的蛋白质中的一些被进一步证实在体外受到调控。因此，我们的研究结果表明，早期增加的肺损伤相关的宿主反应诱导的CK 10可能有助于肺病理和这种病毒在小鼠中的高毒力。
We previously reported a pair of H5N1 avian influenza viruses which are genetically similar but differ greatly in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly lethal to mice, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is avirulent. In this study, to investigate the host factors that account for their virulence discrepancy, we compared the pathology and host proteome of the CK10- or GS10-infected mouse lung. Moderate lung injury was observed from CK10-infected animals as early as the first day of infection, and the pathology steadily progressed at later time point. However, only mild lesions were observed in GS10-infected mouse lung at the late infection stage. Using the quantitative iTRAQ coupled LC–MS/MS method, we first found that more significantly differentially expressed (DE) proteins were stimulated by GS10 compared with CK10. However, bio-function analysis of the DE proteins suggested that CK10 induced much stronger inflammatory response-related functions than GS10. Canonical pathway analysis also demonstrated that CK10 highly activated the “Acute Phase Response Signaling,” which results in a wide range of biological activities in response to viral infection, including many inflammatory processes. Further in-depth analysis showed that CK10 exacerbated acute lung injury-associated responses, including inflammatory response, cell death, reactive oxygen species production and complement response. In addition, some of these identified proteins that associated with the lung injury were further confirmed to be regulated in vitro. Therefore, our findings suggest that the early increased lung injury-associated host response induced by CK10 may contribute to the lung pathology and the high virulence of this virus in mice.