近日，國際著名雜志Hepatology（IF：10.885）在線刊登了武漢大學生命科學學院朱應教授研究組的最新研究成果“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進展,，研究結果通訊作者為朱應教授，第一作者為2008級博士生劉實,。
病毒感染引起機體炎癥應答,，炎癥反應是宿主抵抗病毒感染的本能反應，在清除病毒感染過程中起重要作用,。但炎癥反應是雙刃劍,，過度的炎癥反應導致疾病和死亡。因此,，炎癥因子的表達在體內(nèi)受精細調控,。在2012年，朱應研究組發(fā)現(xiàn)了A型流感病毒侵染能夠通過MicroRNA29上調環(huán)加氧酶II（COX-2）基因的表達并引發(fā)炎癥,。而COX-2通過誘導Ⅲ型干擾素（IFN-λ1）抑制A型流感病毒復制（J Virol 2012,；86：1010-1020）。朱應研究組還發(fā)現(xiàn)了流感病毒通過COX-2和蛋白激酶A信號通路上調白介素27的表達,，白介素27通過類似干擾素的方式抗A型流感病毒感染,。
在這項最新研究中，朱應研究組首次發(fā)現(xiàn)了丙型肝炎病毒能誘導主要穹隆蛋白表達,，而主要穹隆蛋白能通過促進轉錄因子（IRF7/NF-κB）入核來誘導Ⅰ型干擾素的分泌，進而抑制丙型肝炎病毒的復制,。進一步研究發(fā)現(xiàn),，水泡性口炎病毒、A型流感病毒,、腸道病毒71均能誘導主要穹隆蛋白表達,，而主要穹隆蛋白對三種病毒都有抑制作用。該項研究首次闡述了主要穹隆蛋白在病毒感染引起的宿主免疫應答中的作用,，為抗病毒藥物的研究開發(fā)奠定理論基礎,。（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.
