近日，国际著名杂志Hepatology（IF：10.885）在线刊登了武汉大学生命科学学院朱应教授研究组的最新研究成果“Major Vault Protein： A Virus-Induced Host Factor Against Viral Replication Through the Induction of Type-I Interferon”，文章中，研究者揭示了在宿主抗病毒感染方面取得的重要进展，研究结果通讯作者为朱应教授，第一作者为2008级博士生刘实。
病毒感染引起机体炎症应答，炎症反应是宿主抵抗病毒感染的本能反应，在清除病毒感染过程中起重要作用。但炎症反应是双刃剑，过度的炎症反应导致疾病和死亡。因此，炎症因子的表达在体内受精细调控。在2012年，朱应研究组发现了A型流感病毒侵染能够通过MicroRNA29上调环加氧酶II（COX-2）基因的表达并引发炎症。而COX-2通过诱导Ⅲ型干扰素（IFN-λ1）抑制A型流感病毒复制（J Virol 2012；86：1010-1020）。朱应研究组还发现了流感病毒通过COX-2和蛋白激酶A信号通路上调白介素27的表达，白介素27通过类似干扰素的方式抗A型流感病毒感染。
在这项最新研究中，朱应研究组首次发现了丙型肝炎病毒能诱导主要穹隆蛋白表达，而主要穹隆蛋白能通过促进转录因子（IRF7/NF-κB）入核来诱导Ⅰ型干扰素的分泌，进而抑制丙型肝炎病毒的复制。进一步研究发现，水泡性口炎病毒、A型流感病毒、肠道病毒71均能诱导主要穹隆蛋白表达，而主要穹隆蛋白对三种病毒都有抑制作用。该项研究首次阐述了主要穹隆蛋白在病毒感染引起的宿主免疫应答中的作用，为抗病毒药物的研究开发奠定理论基础。（生物谷Bioon.com）
doi:10.1002/hep.25642
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Major vault protein: A virus-induced host factor against viral replication through the induction of type-I interferon
Shi Liu, Qian Hao, Nanfang Peng, Xin Yue, Yu Wang, Yanni Chen, Jianguo Wu, Ying Zhu†,*
Major vault protein (MVP) is the major constituent of vaults and is involved in multidrug resistance, nucleocytoplasmic transport, and cell signaling. However, little is known about the role of MVP during viral infections. In this study, high levels of MVP were found in peripheral blood mononuclear cells, sera, and liver tissue from patients infected with hepatitis C virus (HCV) relative to healthy individuals. HCV infections resulted in elevated levels of MVP mRNA and protein expression in the hepatocyte cell lines Huh7.5.1 and Huh7. Further studies demonstrated that the NF-κB and Sp1 pathways are involved in the induction of MVP expression by HCV. Interestingly, MVP expression suppressed HCV replication and protein synthesis via induction of type-I interferon mRNA expression and protein secretion. Upon investigating the mechanisms behind this event, we found that MVP enhanced the expression of IRF7, but not IRF3. Translocation of activated IRF7 and NF-κB from the cytosol to the nucleus was involved in this process. Furthermore, vesicular stomatitis virus, in?uenza A virus, and enterovirus 71 also induced MVP production, and MVP in turn hampered viral replication and production.
