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

• Published in: Veterinary research (Paris) 2024-09, Vol.55 (1), p.110-14, Article 110
• Main Authors: Xu, Chenxia, Jiang, Yurui, Wang, Mingshu, Cheng, Anchun, Zhang, Wei, Ou, Xumin, Sun, Di, Yang, Qiao, Wu, Ying, Tian, Bin, He, Yu, Wu, Zhen, Zhang, Shaqiu, Zhao, Xinxin, Huang, Juan, Zhu, Dekang, Chen, Shun, Liu, Mafeng, Jia, Renyong
• Format: Article
• Language: English
• Subjects: 3Dpol; Animals; Binding proteins; Development and progression; DHAV-1; Diseases; Ducks; Genetic aspects; Health aspects; Hepatitis A; Hepatitis A virus; Hepatitis Virus, Duck - genetics; Hepatitis Virus, Duck - physiology; Hepatitis, Viral, Animal - virology; IRES; Life Sciences; PCBP2; Physiological aspects; Picornaviridae Infections - veterinary; Picornaviridae Infections - virology; Poultry; Poultry Diseases - virology; Protein Biosynthesis; replication; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; translation; Virus Replication
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/s13567-024-01369-9

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 3D . 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.