近日，國(guó)際著名雜志Hepatology（IF：10.885）在線(xiàn)刊登了武漢大學(xué)生命科學(xué)學(xué)院朱應(yīng)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(jìn)展,，研究結(jié)果通訊作者為朱應(yīng)教授，第一作者為2008級(jí)博士生劉實(shí),。
病毒感染引起機(jī)體炎癥應(yīng)答,，炎癥反應(yīng)是宿主抵抗病毒感染的本能反應(yīng)，在清除病毒感染過(guò)程中起重要作用,。但炎癥反應(yīng)是雙刃劍,，過(guò)度的炎癥反應(yīng)導(dǎo)致疾病和死亡。因此,，炎癥因子的表達(dá)在體內(nèi)受精細(xì)調(diào)控,。在2012年，朱應(yīng)研究組發(fā)現(xiàn)了A型流感病毒侵染能夠通過(guò)MicroRNA29上調(diào)環(huán)加氧酶II（COX-2）基因的表達(dá)并引發(fā)炎癥,。而COX-2通過(guò)誘導(dǎo)Ⅲ型干擾素（IFN-λ1）抑制A型流感病毒復(fù)制（J Virol 2012,；86：1010-1020）。朱應(yīng)研究組還發(fā)現(xiàn)了流感病毒通過(guò)COX-2和蛋白激酶A信號(hào)通路上調(diào)白介素27的表達(dá),，白介素27通過(guò)類(lèi)似干擾素的方式抗A型流感病毒感染,。
在這項(xiàng)最新研究中，朱應(yīng)研究組首次發(fā)現(xiàn)了丙型肝炎病毒能誘導(dǎo)主要穹隆蛋白表達(dá),，而主要穹隆蛋白能通過(guò)促進(jìn)轉(zhuǎn)錄因子（IRF7/NF-κB）入核來(lái)誘導(dǎo)Ⅰ型干擾素的分泌,，進(jìn)而抑制丙型肝炎病毒的復(fù)制。進(jìn)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(dǎo)主要穹隆蛋白表達(dá),，而主要穹隆蛋白對(duì)三種病毒都有抑制作用,。該項(xiàng)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(yīng)答中的作用，為抗病毒藥物的研究開(kāi)發(fā)奠定理論基礎(chǔ),。（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.
