Bombyx mori nucleopolyhedrosis virus-derived circular RNAs with protein-coding potential facilitate viral replication

IF 4.3 2区农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Insect Biochemistry and Molecular Biology Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI:10.1016/j.ibmb.2025.104420

Xing Zhang , Zeen Shen , Yani Kang , Wenbin Yu , Xiaoyan Du , Qian Teng , Zihan He , Chengliang Gong , Xiaolong Hu

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Abstract

Circular RNAs (circRNAs) are renowned for their exceptional stability and have been increasingly recognized for their dual roles in pro- and antiviral responses during host-virus interactions. In this study, we investigated the functional landscape of circular RNAs (circRNAs) during infection with Bombyx mori nucleopolyhedrosis virus (BmNPV), a model baculovirus system. Our comprehensive analysis revealed that hundreds of host-derived circRNAs are dynamically regulated upon BmNPV infection, while the virus itself generates numerous viral circRNAs (vcircRNAs) via back-splicing. Using a combination of advanced experimental approaches, we validated the existence of multiple cellular and viral circRNAs. Among these, we characterized vcircRNA-390, a BmNPV-encoded circRNA harboring a small open reading frame (ORF) and four viral internal ribosome entry sites (IRESs). Remarkably, vcircRNA-390 serves as a template for the translation of an 81-amino acid viral peptide (VSP81). Functional studies demonstrated that both vcircRNA-390 and VSP81 significantly enhance viral replication. Mechanistically, we provide evidence that VSP81 likely targets the host RNA interference (RNAi) pathway, a major antiviral defence system, to promote viral immune evasion. While these findings establish vcircRNA-390 as a novel proviral factor in insect-virus interactions, the detailed molecular mechanisms by which VSP81 modulates the RNAi machinery remain to be fully elucidated. Our work not only expands the understanding of viral circRNA biology but also reveals a new dimension of the host-pathogen conflict, wherein BmNPV exploits circRNA-mediated translation to subvert antiviral defences.

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家蚕核多角体病毒衍生的环状rna具有蛋白质编码潜能，可促进病毒复制。

环状rna （circRNAs）以其卓越的稳定性而闻名，并因其在宿主-病毒相互作用期间的亲抗病毒反应中的双重作用而日益得到认可。在这项研究中，我们研究了环状rna （circRNAs）在感染家蚕核多角体病毒（BmNPV）时的功能景观。我们的综合分析显示，数百种宿主衍生的环状rna在BmNPV感染时受到动态调节，而病毒本身通过反剪接产生许多病毒环状rna （vcircRNAs）。结合先进的实验方法，我们验证了多种细胞和病毒环状rna的存在。其中，我们鉴定了vcircRNA-390，这是一种bmnpv编码的环状rna，含有一个小的开放阅读框（ORF）和四个病毒内部核糖体进入位点（IRESs）。值得注意的是，vcircRNA-390可作为81个氨基酸的病毒肽（VSP81）翻译的模板。功能研究表明，vcircRNA-390和VSP81均能显著增强病毒复制。在机制上，我们提供的证据表明，VSP81可能靶向宿主RNA干扰（RNAi）途径，一个主要的抗病毒防御系统，以促进病毒免疫逃避。虽然这些发现确定了vcircRNA-390是昆虫-病毒相互作用中的一个新的原病毒因子，但VSP81调节RNAi机制的详细分子机制仍有待充分阐明。我们的工作不仅扩展了对病毒circRNA生物学的理解，而且揭示了宿主-病原体冲突的一个新维度，其中BmNPV利用circRNA介导的翻译来破坏抗病毒防御。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Insect Biochemistry and Molecular Biology 生物-昆虫学

CiteScore

7.40

自引率

5.30%

发文量

105

审稿时长

40 days

期刊介绍： This international journal publishes original contributions and mini-reviews in the fields of insect biochemistry and insect molecular biology. Main areas of interest are neurochemistry, hormone and pheromone biochemistry, enzymes and metabolism, hormone action and gene regulation, gene characterization and structure, pharmacology, immunology and cell and tissue culture. Papers on the biochemistry and molecular biology of other groups of arthropods are published if of general interest to the readership. Technique papers will be considered for publication if they significantly advance the field of insect biochemistry and molecular biology in the opinion of the Editors and Editorial Board.