Down-regulated TAB1 suppresses the replication of Coxsackievirus B5 via activating the NF-κB pathways through interaction with viral 3D polymerase

• Published in: Virology journal Vol. 20; no. 1; p. 291
• Main Authors: Zhang, Jiayu, Teng, Peiying, Sun, Bo, Zhang, Jihong, Zhou, Xiaoshuang, Chen, Wei
• Format: Journal Article
• Language: English
• Published: England BioMed Central 10.12.2023; BMC
• Subjects: 3D polymerase; Antibodies; Cell adhesion; Cloning; Coxsackievirus; Coxsackievirus group B type 5 (CVB5); Coxsackieviruses; Cytokines; DNA-directed RNA polymerase; Genomes; Hand-foot-and-mouth disease; Hand-foot-mouth disease (HFMD); Immune response; Immunoprecipitation; Infections; Inflammation; Innate immunity; Kinases; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Meningitis; Movement disorders; Neurodegenerative diseases; Neurological complications; NF-κB protein; Nuclear factor kappa-B (NF-κB) pathway; Parkinson's disease; Peptides; Phosphatase; Phosphorylation; Plasmids; Proteins; Public health; Replication; RNA-directed RNA polymerase; Scientific imaging; Software; Structure-function relationships; TGF-BATA-activated kinase1 binding protein 1 (TAB1); Viral infections; Viruses; United States > US; China; Nuclear factor kappa-B (NF-κB) pathway; Coxsackievirus group B type 5 (CVB5); Hand-foot-mouth disease (HFMD); 3D polymerase; TGF-BATA-activated kinase1 binding protein 1 (TAB1)
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-023-02259-w

Coxsackievirus Group B type 5 (CVB5), an important pathogen of hand-foot-mouth disease, is also associated with neurological complications and poses a public health threat to young infants. Among the CVB5 proteins, the nonstructural protein 3D, known as the Enteroviral RNA-dependent RNA polymerase, is mainly involved in viral genome replication and transcription. In this study, we performed immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify host proteins that interacted with CVB5 3D polymerase. A total of 116 differentially expressed proteins were obtained. Gene Ontology analysis identified that the proteins were involved in cell development and cell adhesion, distributed in the desmosome and envelope, and participated in GTPase binding. Kyoto Encyclopedia of Genes and Genomes analysis further revealed they participated in nerve diseases, such as Parkinson disease. Among them, 35 proteins were significantly differentially expressed and the cellular protein TGF-BATA-activated kinase1 binding protein 1 (TAB1) was found to be specifically interacting with the 3D polymerase. 3D polymerase facilitated the entry of TAB1 into the nucleus and down-regulated TAB1 expression via the lysosomal pathway. In addition, TAB1 inhibited CVB5 replication via inducing inflammatory factors and activated the NF-κB pathway through IκBα phosphorylation. Moreover, the 90-96aa domain of TAB1 was an important structure for the function. Collectively, our findings demonstrate the mechanism by which cellular TAB1 inhibits the CVB5 replication via activation of the host innate immune response, providing a novel insight into the virus-host innate immunity.