Canine parvovirus NS1 induces host translation shutoff by reducing mTOR phosphorylation.

IF 4 2区 医学 Q2 VIROLOGY Journal of Virology Pub Date : 2024-11-27 DOI:10.1128/jvi.01463-24
Xinrui Wang, Xiangqi Hao, Yaning Zhao, Xiangyu Xiao, Shoujun Li, Pei Zhou
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Abstract

Canine parvovirus type 2 (CPV-2) is a member of the Parvoviridae family, characterized by its small, non-enveloped virions containing a linear single-stranded DNA genome of approximately 5 kb. Parvoviruses entirely reliant on the host cell's division machinery for replication. In this study, we demonstrate that CPV-2 infection triggers the host translation shutoff, a process in which the nonstructural protein 1 (NS1) plays a pivotal role. Our findings indicate that the CPV-2 NS1-induced host translation shutoff is not associated with transcription, protein degradation pathways, or eIFα phosphorylation, but rather involves the reduction of phosphorylation of the mammalian target of rapamycin (mTOR). In conclusion, this research reveals that CPV-2 NS1 induces a host translation shutoff by reducing mTOR phosphorylation, a mechanism that could potentially inform the development of more efficacious control and therapeutic strategies for CPV-2 and other parvoviral infections.

Importance: Autonomous parvoviruses, which possess compact genomes, are obligate intracellular parasites that necessitate host cell division for their replication cycle. Consequently, the modulation of host translation and usurpation of cellular machinery are hypothesized to facilitate immune evasion, enhance viral transmission, and perpetuate long-term infection. Despite the biological significance, the precise mechanisms by which autonomous parvoviruses regulate host translation remain understudied. Our study elucidates that CPV-2 infection induces a shutoff of host translation through the attenuation of mTOR phosphorylation. This mechanism may enable the virus to subvert the host immune response and engender pathogenic effects.

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犬细小病毒 NS1 通过减少 mTOR 磷酸化诱导宿主翻译关闭。
犬细小病毒 2 型(CPV-2)是细小病毒科的一员,其特点是病毒小而无包膜,含有约 5 kb 的线性单链 DNA 基因组。副病毒完全依赖宿主细胞的分裂机制进行复制。在本研究中,我们证明了 CPV-2 感染会触发宿主翻译关闭,而在这一过程中,非结构蛋白 1(NS1)起着关键作用。我们的研究结果表明,CPV-2 NS1 诱导的宿主翻译关闭与转录、蛋白质降解途径或 eIFα 磷酸化无关,而是涉及雷帕霉素哺乳动物靶标(mTOR)磷酸化的减少。总之,这项研究揭示了 CPV-2 NS1 通过降低 mTOR 磷酸化诱导宿主翻译关闭,这一机制有可能为 CPV-2 和其他副病毒感染开发更有效的控制和治疗策略提供信息:自主副病毒拥有紧凑的基因组,是一种强制性细胞内寄生虫,其复制周期需要宿主细胞分裂。因此,对宿主翻译的调控和对细胞机制的篡夺被假定为有助于免疫逃避、增强病毒传播和维持长期感染。尽管具有生物学意义,但自主副病毒调节宿主翻译的确切机制仍未得到充分研究。我们的研究阐明,CPV-2 感染可通过抑制 mTOR 磷酸化诱导宿主翻译的关闭。这种机制可能使病毒能够颠覆宿主的免疫反应并产生致病作用。
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
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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