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单链RNA病毒蛋白的磷酸化及新型治疗策略的潜力

Phosphorylation of Single Stranded RNA Virus Proteins and Potential for Novel Therapeutic Strategies.

作者信息

Keck Forrest, Ataey Pouya, Amaya Moushimi, Bailey Charles, Narayanan Aarthi

机构信息

National Center for Biodefense and Infectious Disease, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA 20110, USA.

出版信息

Viruses. 2015 Oct 12;7(10):5257-73. doi: 10.3390/v7102872.

Abstract

Post translational modification of proteins is a critical requirement that regulates function. Among the diverse kinds of protein post translational modifications, phosphorylation plays essential roles in protein folding, protein:protein interactions, signal transduction, intracellular localization, transcription regulation, cell cycle progression, survival and apoptosis. Protein phosphorylation is also essential for many intracellular pathogens to establish a productive infection cycle. Preservation of protein phosphorylation moieties in pathogens in a manner that mirrors the host components underscores the co-evolutionary trajectory of pathogens and hosts, and sheds light on how successful pathogens have usurped, either in part or as a whole, the host enzymatic machinery. Phosphorylation of viral proteins for many acute RNA viruses including Flaviviruses and Alphaviruses has been demonstrated to be critical for protein functionality. This review focuses on phosphorylation modifications that have been documented to occur on viral proteins with emphasis on acutely infectious, single stranded RNA viruses. The review additionally explores the possibility of repurposing Food and Drug Administration (FDA) approved inhibitors as antivirals for the treatment of acute RNA viral infections.

摘要

蛋白质的翻译后修饰是调节功能的关键要求。在多种多样的蛋白质翻译后修饰中,磷酸化在蛋白质折叠、蛋白质-蛋白质相互作用、信号转导、细胞内定位、转录调控、细胞周期进程、存活和凋亡中发挥着重要作用。蛋白质磷酸化对于许多细胞内病原体建立有效的感染周期也至关重要。以反映宿主成分的方式保留病原体中的蛋白质磷酸化部分,凸显了病原体和宿主的共同进化轨迹,并揭示了成功的病原体如何部分或全部篡夺宿主的酶促机制。对于包括黄病毒和甲病毒在内的许多急性RNA病毒,病毒蛋白的磷酸化已被证明对蛋白质功能至关重要。本综述重点关注已记录在病毒蛋白上发生的磷酸化修饰,重点是急性感染性单链RNA病毒。该综述还探讨了将美国食品药品监督管理局(FDA)批准的抑制剂重新用作抗病毒药物以治疗急性RNA病毒感染的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0b/4632380/7a4632bd0009/viruses-07-02872-g001.jpg

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