Host cell substrates of RNA virus proteases

RNA病毒蛋白酶的宿主细胞底物

• 批准号: RGPIN-2017-04515
• 负责人: Jan, Eric
• 金额: $ 3.64万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629751
• 关键词: Host; cell; substrates; RNA; virus

Dicistroviruses are RNA viruses that mainly infect arthropods and have had a negative impact of agriculture and economic importance. Members include the honeybee viruses that have been associated with honeybee disease and the Taura syndrome virus, which has led to disease outbreaks in the panaeid shrimp industry. To date, the life cycle and virus host interactions are not fully understood and thus, has impacted our understanding of these viruses and limited potential antiviral strategies. However, infection of Drosophila (fruit fly) by the model dicistrovirus cricket paralysis virus (CrPV) has been instrumental in deciphering key processes into how dicistroviruses commandeer the host cell. One of the signature properties of dicistroviruses is that the virus expresses a protein, called a protease, which cleaves host proteins in the cell to facilitate virus infection. Currently, the extent of host proteins targeted by the viral protease is not known. In this study, we will utilize a novel unbiased proteomics approach called TAILS to comprehensively identify all of the targets of the dicistrovirus CrPV protease in Drosophila cells. Unlike other methods, this new TAILS approach is sensitive and can identify the location of the cleavage site on the target protein. The identification of novel targets will provide a catalog of the host processes that are affected during dicistrovirus infection. Importantly, the knowledge gained will allow us to identify new targets for antiviral therapy. The development of this strategy can be exploited to identify the repertoire of host targets of proteases from other viruses, ultimately leading to better treatment protocols for a range of virus infections causing pathological disease.

双虫病毒是主要感染节肢动物的RNA病毒，对农业和经济具有重要的负面影响。成员包括与蜜蜂疾病有关的蜜蜂病毒和陶拉综合症病毒，这种病毒导致了panaeid对虾业的疾病爆发。迄今为止，生命周期和病毒宿主相互作用尚未完全了解，因此，影响了我们对这些病毒的理解并限制了潜在的抗病毒策略。然而，由模型双侧病毒蟋蟀麻痹病毒（CrPV）感染果蝇（果蝇）有助于破译双侧病毒如何占领宿主细胞的关键过程。双异状病毒的一个特征是，这种病毒表达一种叫做蛋白酶的蛋白质，这种蛋白质在细胞中切割宿主蛋白质，以促进病毒感染。目前，病毒蛋白酶靶向宿主蛋白的程度尚不清楚。在这项研究中，我们将利用一种名为TAILS的新型无偏蛋白质组学方法来全面鉴定果蝇细胞中二叉病毒CrPV蛋白酶的所有靶标。与其他方法不同，这种新的TAILS方法是敏感的，可以识别目标蛋白上切割位点的位置。新靶标的鉴定将提供在双链病毒感染期间受影响的宿主进程的目录。重要的是，获得的知识将使我们能够确定抗病毒治疗的新靶点。这一策略的发展可以用来鉴定来自其他病毒的蛋白酶的宿主靶点，最终导致更好的治疗方案，用于一系列引起病理疾病的病毒感染。