ABSTRACT

Circular RNAs (circRNAs) are ubiquitously expressed, covalently closed rings, produced by pre-mRNA splicing in a reversed order during post-transcriptional processing. Circularity endows 3′-5′-linked circRNAs with stability and resistance to exonucleolytic degradation which raises the question whether circRNAs may be relevant as potential therapeutic targets or agents. High stability in biological systems is the most remarkable property and a major criterion for why circRNAs could be exploited for a range of RNA-centred medical applications. Even though various biological roles and regulatory functions of circRNAs have been reported, their in-depth study is challenging because of their circular structure and sequence-overlap with linear mRNA counterparts. Moreover, little is known about their role in viral infections and in antiviral immune responses. We believe that an in-depth and detailed understanding of circRNA mediated viral protein regulations will increase our knowledge of the biology of these novel molecules. In this review, we aimed to provide a comprehensive basis and overview on the biogenesis, significance and regulatory roles of circRNAs in the context of antiviral immune responses and viral infections including hepatitis C virus infection, hepatitis B virus infection, hepatitis delta virus infection, influenza A virus infection, Epstein-Barr virus infection, kaposi’s sarcoma herpesvirus infection, human cytomegalovirus infection, herpes simplex virus infection, human immunodeficiency virus infection, porcine epidemic diarrhoea virus infection, ORF virus infection, avian leukosis virus infection, simian vacuolating virus 40 infection, transmissible gastroenteritis coronavirus infection, and bovine viral diarrhoea virus infection. We have also discussed the critical regulatory role of circRNAs in provoking antiviral immunity, providing evidence for implications as therapeutic agents and as diagnostic markers.

摘要

环状RNA（circRNA）在转录后加工过程中以相反的顺序通过逆转录顺序普遍表达，即共价闭合的环。圆形性赋予3'-5'连接的circRNA稳定和对核酸外切降解的抵抗力，这提出了circRNA是否可能作为潜在治疗靶标或药物相关的问题。生物系统中的高稳定性是最显着的特性，也是为什么可以将circRNA用于以RNA为中心的一系列医疗应用的主要标准。尽管已经报道了circRNA的各种生物学作用和调节功能，但由于其环状结构和与线性mRNA对应物的序列重叠，因此对其进行深入研究仍具有挑战性。此外，关于它们在病毒感染和抗病毒免疫反应中的作用知之甚少。我们相信，对circRNA介导的病毒蛋白调控的深入和详细的了解将增加我们对这些新型分子生物学的了解。在这篇综述中，我们旨在提供全面的基础和概述circRNA在抗病毒免疫反应和病毒感染（包括丙型肝炎病毒感染，乙型肝炎病毒感染，丙型肝炎三角洲病毒感染，流感）中的生物发生，意义和调控作用。病毒感染，爱泼斯坦-巴尔病毒感染，卡波济肉瘤疱疹病毒感染，人巨细胞病毒感染，单纯疱疹病毒感染，人免疫缺陷病毒感染，猪流行性腹泻病毒感染，ORF病毒感染，禽白血病病毒感染，猿猴空泡病毒40感染，传染性胃肠炎冠状病毒感染和牛病毒性腹泻病毒感染。我们还讨论了circRNA在激发抗病毒免疫中的关键调控作用，为作为治疗剂和诊断标志物的意义提供了证据。