关键词: baculovirus gene regulation miRNA

Mesh : Nucleopolyhedroviruses / genetics Animals MicroRNAs / genetics metabolism Virus Replication Gene Expression Regulation, Viral Viral Proteins / genetics metabolism Larva / virology genetics Sf9 Cells Viral Load Spodoptera / virology Virion / genetics metabolism

来  源:   DOI:10.1128/jvi.00570-24   PDF(Pubmed)

Abstract:
Virus-encoded microRNAs (miRNAs) exert diverse regulatory roles in the biological processes of both viruses and hosts. This study delves into the functions of AcMNPV-miR-2, an early miRNA encoded by Autographa californica multiple nucleopolyhedrovirus (AcMNPV). AcMNPV-miR-2 targets viral early genes ac28 (lef-6), ac37 (lef-11), ac49, and ac63. Overexpression of AcMNPV-miR-2 leads to reduced production of infectious budded virions (BVs) and diminished viral DNA replication. Delayed polyhedron formation was observed through light and transmission electron microscopy, and the larval lifespan extended in oral infection assays. Moreover, the mRNA expression levels of two Lepidoptera-specific immune-related proteins, Gloverin and Spod-11-tox, significantly decreased. These findings indicate that AcMNPV-miR-2 restrains viral load, reducing host immune sensitivity. This beneficial effect enables the virus to combat host defense mechanisms and reside within the host for an extended duration.
OBJECTIVE: Virus-encoded miRNAs have been extensively studied for their pivotal roles in finetuning viral infections. Baculoviruses, highly pathogenic in insects, remain underexplored concerning their encoded miRNAs. Previous reports outlined three AcMNPV-encoded miRNAs, AcMNPV-miR-1, -miR-3, and -miR-4. This study delves into the functions of another AcMNPV-encoded miRNA, AcMNPV-miR-2 (Ac-miR-2). Through a comprehensive analysis of target gene expression, the impact on larvae, and variations in host immune-related gene expression, we elucidate a functional pathway for Ac-miR-2. This miRNA suppresses viral load and infectivity and prolongs lifespans of infected larva by downregulating specific viral early genes and host immune-related genes. These mechanisms ultimately serve the virus\'s primary goal of enhanced propagation. Our study significantly contributes to understanding of the intricate regulatory mechanisms of virus-encoded miRNAs in baculovirus infections.
摘要:
病毒编码的microRNAs(miRNAs)在病毒和宿主的生物过程中发挥不同的调节作用。这项研究探讨了AcMNPV-miR-2的功能,AcMNPV-2是由加利福尼亚多核多角体病毒(AcMNPV)编码的早期miRNA。AcMNPV-miR-2靶向病毒早期基因ac28(lef-6),AC37(LEF-11),ac49和ac63。AcMNPV-miR-2的过表达导致感染性芽病毒体(BV)的产生减少和病毒DNA复制减少。通过光学和透射电子显微镜观察到延迟的多面体形成,在口腔感染试验中,幼虫寿命延长。此外,两种鳞翅目特异性免疫相关蛋白的mRNA表达水平,Gloverin和Spod-11-tox,显著下降。这些结果表明,AcMNPV-miR-2抑制病毒载量,降低宿主免疫敏感性。这种有益效果使得病毒能够对抗宿主防御机制并在宿主内驻留延长的持续时间。
目的:已广泛研究了病毒编码的miRNA在微调病毒感染中的关键作用。杆状病毒,昆虫的高致病性,对其编码的miRNA仍未充分研究。以前的报告概述了三种AcMNPV编码的miRNA,AcMNPV-miR-1、-miR-3和-miR-4。本研究深入研究了另一个AcMNPV编码的miRNA的功能,AcMNPV-miR-2(Ac-miR-2)。通过对靶基因表达的综合分析,对幼虫的影响,以及宿主免疫相关基因表达的变化,我们阐明了Ac-miR-2的功能通路。该miRNA通过下调特定的病毒早期基因和宿主免疫相关基因来抑制病毒载量和感染性并延长受感染幼虫的寿命。这些机制最终服务于病毒增强传播的主要目标。我们的研究显著有助于理解杆状病毒感染中病毒编码的miRNA的复杂调控机制。
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