YBX1 is required for assembly of viral replication complexes of chikungunya virus and replication of multiple alphaviruses.

IF 4 2区 医学 Q2 VIROLOGY
Journal of Virology Pub Date : 2025-02-25 Epub Date: 2024-12-31 DOI:10.1128/jvi.02015-24
Zhen-Qi Li, Li-Xin Zhao, Su-Yun Wang, Chu-Yu Hu, Yan-Yi Wang, Yan Yang
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引用次数: 0

Abstract

Chikungunya virus (CHIKV), an enveloped positive-sense RNA virus, is a member of the alphaviruses and cause fever and arthralgia in humans. We performed genome-wide CRISPR/Cas9-based screens and identified Y-box binding protein 1 (YBX1) as an essential cellular factor for CHIKV. Deficiency of YBX1 inhibited CHIKV RNA replication and impaired virus production. Upon CHIKV infection, YBX1 showed a striking re-localization to viral replication complexes (vRCs), where it co-localized with CHIKV nsP3 and dsRNA intermediates. YBX1 directly interacted with CHIKV nsP3, and mutation of the YBX1-binding motif in CHIKV nsP3 suppressed viral replication in host cells. Furthermore, YBX1 bound to viral RNA and increased the viral RNA-binding activity of CHIKV nsP3. Consistently, the RNA-binding activity of YBX1, as well as the ability of nsP3 to bind to YBX1, was required for efficient CHIKV replication. In addition to CHIKV, YBX1 was also essential for replication of all examined alphaviruses including the prototypic alphavirus. Our findings suggest that YBX1 acts as a scaffold for assembly of chikungunya vRCs and an important factor for replication of multiple alphaviruses, which may serve as a potential target for the development of anti-alphavirus therapies.IMPORTANCEAlphaviruses are a group of mosquito-transmitted, enveloped, positive-strand RNA viruses in the Togaviridae family. Most alphaviruses are important pathogens that continue to cause human disease ranging from severe and potentially fatal neurological disease to chronic arthritic disease on a global scale. Here, we found that YBX1 promotes binding of CHIKV genomic RNA to nsP3, which is a key component of the replication complex, and is therefore pivotal for CHIKV replication. Deficiency of YBX1 results in reduced replication of multiple alphaviruses, including arthritogenic and encephalitic alphaviruses. These findings suggest that YBX1 is an important cellular factor for multiple alphaviruses and a potential target for preventing alphavirus infections.

YBX1是基孔肯雅病毒复制复合体的组装和多种甲病毒复制所必需的。
基孔肯雅病毒(CHIKV)是一种包膜正义RNA病毒,是甲病毒的一员,可引起人类发烧和关节痛。我们进行了基于CRISPR/ cas9的全基因组筛选,发现Y-box结合蛋白1 (YBX1)是CHIKV的必要细胞因子。缺乏YBX1抑制了CHIKV RNA的复制和病毒的产生。在CHIKV感染后,YBX1表现出惊人的病毒复制复合体(vRCs)的重新定位,在那里它与CHIKV nsP3和dsRNA中间体共定位。YBX1直接与CHIKV nsP3相互作用,CHIKV nsP3中YBX1结合基序的突变抑制了病毒在宿主细胞中的复制。此外,YBX1与病毒RNA结合,提高了CHIKV nsP3的病毒RNA结合活性。同样,YBX1的rna结合活性以及nsP3与YBX1结合的能力是CHIKV高效复制所必需的。除CHIKV病毒外,YBX1病毒对所有检测的甲病毒(包括原型甲病毒)的复制也是必不可少的。我们的研究结果表明,YBX1作为基孔肯雅vRCs组装的支架和多种甲病毒复制的重要因子,可能成为开发抗甲病毒疗法的潜在靶点。甲病毒是托加病毒科一组由蚊子传播的包膜正链RNA病毒。大多数甲病毒是重要的病原体,继续在全球范围内引起人类疾病,从严重和可能致命的神经疾病到慢性关节炎疾病。在这里,我们发现YBX1促进CHIKV基因组RNA与nsP3的结合,nsP3是复制复合体的关键成分,因此对CHIKV复制至关重要。缺乏YBX1导致多种甲病毒的复制减少,包括关节炎性和脑炎性甲病毒。这些发现表明YBX1是多种甲病毒的重要细胞因子,也是预防甲病毒感染的潜在靶点。
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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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