Duck hepatitis A virus utilizes PCBP2 to facilitate viral translation and replication

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES Veterinary Research Pub Date : 2024-09-19 DOI:10.1186/s13567-024-01369-9
Chenxia Xu, Yurui Jiang, Mingshu Wang, Anchun Cheng, Wei Zhang, Xumin Ou, Di Sun, Qiao Yang, Ying Wu, Bin Tian, Yu He, Zhen Wu, Shaqiu Zhang, Xinxin Zhao, Juan Huang, Dekang Zhu, Shun Chen, Mafeng Liu, Renyong Jia
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Abstract

Duck hepatitis A virus type 1 (DHAV-1) is an important member of the Picornaviridae family that causes highly fatal hepatitis in ducklings. Since picornaviruses have small genomes with limited coding capacity, they must utilize host proteins for viral cap-independent translation and RNA replication. Here, we report the role of duck poly(rC)-binding protein 2 (PCBP2) in regulating the replication and translation of DHAV-1. During DHAV-1 infection, PCBP2 expression was upregulated. A biotinylated RNA pull-down assay revealed that PCBP2 positively regulates DHAV-1 translation through specific interactions with structural domains II and III of the DHAV-1 internal ribosome entry site (IRES). Further studies revealed that PCBP2 promotes DHAV-1 replication via an interaction of its KH1 domain (aa 1–92) with DHAV-1 3Dpol. Thus, our studies demonstrated the specific role of PCBP2 in regulating DHAV-1 translation and replication, revealing a novel mechanism by which host‒virus interactions regulate viral translation and replication. These findings contribute to further understanding of the pathogenesis of picornavirus infections.
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鸭甲型肝炎病毒利用 PCBP2 促进病毒翻译和复制
鸭甲型肝炎病毒 1 型(DHAV-1)是短小病毒科(Picornaviridae)的一个重要成员,可导致雏鸭发生高度致命的肝炎。由于短小病毒的基因组较小,编码能力有限,因此它们必须利用宿主蛋白进行病毒帽无关翻译和 RNA 复制。在此,我们报告了鸭多聚(rC)结合蛋白 2(PCBP2)在调节 DHAV-1 复制和翻译中的作用。在 DHAV-1 感染期间,PCBP2 的表达上调。生物素化 RNA 拉低试验显示,PCBP2 通过与 DHAV-1 内部核糖体进入位点(IRES)的结构域 II 和 III 的特异性相互作用,对 DHAV-1 的翻译起着积极的调控作用。进一步的研究发现,PCBP2 通过其 KH1 结构域(aa 1-92)与 DHAV-1 3Dpol 的相互作用促进了 DHAV-1 的复制。因此,我们的研究证明了 PCBP2 在调节 DHAV-1 翻译和复制中的特殊作用,揭示了宿主-病毒相互作用调节病毒翻译和复制的新机制。这些发现有助于进一步了解皮卡病毒感染的发病机制。
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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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