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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=654496
• 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.

双切病毒是主要感染节肢动物的RNA病毒，并且对农业和经济重要性产生了负面影响。成员包括与蜜蜂疾病和陶拉综合症病毒有关的蜜蜂病毒，这导致了Panaeid Shrimp行业的疾病爆发。迄今为止，生命周期和病毒宿主相互作用尚未完全理解，因此影响了我们对这些病毒的理解和有限的潜在抗病毒药策略。然而，模型dicistrovirus板球瘫痪病毒（CRPV）对果蝇（果蝇）的感染一直在将关键过程解密到dicistroviruses命令中的宿主细胞中。双肌病毒的特性之一是该病毒表达一种称为蛋白酶的蛋白质，该蛋白质会在细胞中切割宿主蛋白，以促进病毒感染。目前，尚不清楚由病毒蛋白酶靶向的宿主蛋白的程度。在这项研究中，我们将利用一种称为Tails的新型无偏蛋白质组学方法来全面识别果蝇细胞中二炎病毒CRPV蛋白酶的所有靶标。与其他方法不同，这种新的尾巴方法是敏感的，可以识别裂解位点在靶蛋白上的位置。新靶标的识别将提供宿主过程中受影响的宿主过程的目录。重要的是，获得的知识将使我们能够确定抗病毒疗法的新靶标。可以利用该策略的发展来确定其他病毒蛋白酶宿主靶标的曲目，最终导致了一系列病毒感染的更好的治疗方案，从而导致病理疾病。