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虫媒病毒的持续适应性挑战:一种鉴定保守病毒 RNA 序列与宿主 RNA 结合蛋白 (RBPs) 之间可能相互作用的计算方法。

The Continuous Adaptive Challenge Played by Arboviruses: An In Silico Approach to Identify a Possible Interplay between Conserved Viral RNA Sequences and Host RNA Binding Proteins (RBPs).

机构信息

U.O.C. Medical and Laboratory Genetics, A.O.R.N., Cardarelli, 80131 Naples, Italy.

Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84084 Baronissi, SA, Italy.

出版信息

Int J Mol Sci. 2023 Jul 4;24(13):11051. doi: 10.3390/ijms241311051.

Abstract

Climate change and globalization have raised the risk of vector-borne disease (VBD) introduction and spread in various European nations in recent years. In Italy, viruses carried by tropical vectors have been shown to cause viral encephalitis, one of the symptoms of arboviruses, a spectrum of viral disorders spread by arthropods such as mosquitoes and ticks. Arboviruses are currently causing alarm and attention, and the World Health Organization (WHO) has released recommendations to adopt essential measures, particularly during the hot season, to restrict the spreading of the infectious agents among breeding stocks. In this scenario, rapid analysis systems are required, because they can quickly provide information on potential virus-host interactions, the evolution of the infection, and the onset of disabling clinical symptoms, or serious illnesses. Such systems include bioinformatics approaches integrated with molecular evaluation. Viruses have co-evolved different strategies to transcribe their own genetic material, by changing the host's transcriptional machinery, even in short periods of time. The introduction of genetic alterations, particularly in RNA viruses, results in a continuous adaptive fight against the host's immune system. We propose an in silico pipeline method for performing a comprehensive motif analysis (including motif discovery) on entire genome sequences to uncover viral sequences that may interact with host RNA binding proteins (RBPs) by interrogating the database of known RNA binding proteins, which play important roles in RNA metabolism and biological processes. Indeed, viral RNA sequences, able to bind host RBPs, may compete with cellular RNAs, altering important metabolic processes. Our findings suggest that the proposed in silico approach could be a useful and promising tool to investigate the complex and multiform clinical manifestations of viral encephalitis, and possibly identify altered metabolic pathways as targets of pharmacological treatments and innovative therapeutic protocols.

摘要

气候变化和全球化导致近年来各种欧洲国家的虫媒传染病(VBD)传入和传播风险增加。在意大利,已经证实热带媒介携带的病毒会导致病毒性脑炎,这是虫媒病毒病的一种症状,是一种由蚊子和蜱等节肢动物传播的病毒疾病谱。虫媒病毒病目前引起了警报和关注,世界卫生组织(WHO)发布了建议,采取必要措施,特别是在炎热季节,限制传染病在繁殖种群中的传播。在这种情况下,需要快速分析系统,因为它们可以快速提供有关潜在病毒-宿主相互作用、感染演变以及出现致残临床症状或严重疾病的信息。此类系统包括与分子评估相结合的生物信息学方法。病毒已经进化出不同的策略来转录自己的遗传物质,通过改变宿主的转录机制,即使在短时间内也是如此。遗传改变的引入,特别是在 RNA 病毒中,导致了与宿主免疫系统的持续适应性斗争。我们提出了一种基于计算的管道方法,用于对整个基因组序列进行全面的基序分析(包括基序发现),以通过查询已知 RNA 结合蛋白数据库来发现可能与宿主 RNA 结合蛋白(RBPs)相互作用的病毒序列,这些蛋白在 RNA 代谢和生物学过程中发挥重要作用。事实上,能够与宿主 RBPs 结合的病毒 RNA 序列可能会与细胞 RNA 竞争,改变重要的代谢过程。我们的研究结果表明,所提出的计算方法可能是一种有用且有前途的工具,可以研究病毒性脑炎的复杂和多样的临床表现,并可能确定改变的代谢途径作为药物治疗和创新治疗方案的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14c/10341531/227e64367e91/ijms-24-11051-g001.jpg

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