TRIM56 restricts Coxsackievirus B infection by mediating the ubiquitination of viral RNA-dependent RNA polymerase 3D.

Autor: Wang Y; Department of Cell Biology, Harbin Medical University, Harbin, China., Dong Y; Department of Cell Biology, Harbin Medical University, Harbin, China., Luan T; Department of Cell Biology, Harbin Medical University, Harbin, China., Chen Y; Department of Microbiology, Harbin Medical University, Harbin, China., Lin L; Teaching Center of Pathogenic Biology, Harbin Medical University, Harbin, China., Li S; Department of Cell Biology, Harbin Medical University, Harbin, China., Feng D; Department of Cell Biology, Harbin Medical University, Harbin, China., Wei J; Department of Cell Biology, Harbin Medical University, Harbin, China., Fei Y; Department of Microbiology, Harbin Medical University, Harbin, China., Wang G; Teaching Center of Pathogenic Biology, Harbin Medical University, Harbin, China., Pan J; Department of Cell Biology, Harbin Medical University, Harbin, China., Wang Y; Department of Microbiology, Harbin Medical University, Harbin, China., Zhong Z; Department of Microbiology, Harbin Medical University, Harbin, China., Zhao W; Department of Cell Biology, Harbin Medical University, Harbin, China.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Sep 30; Vol. 20 (9), pp. e1012594. Date of Electronic Publication: 2024 Sep 30 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012594
Abstrakt: Coxsackievirus B (CVB) is the major causative pathogen for severe diseases such as viral myocarditis, meningitis, and pancreatitis. There is no effective antiviral therapy currently available for CVB infection primarily due to that the pathogenesis of CVB has not been completely understood. Viruses are obligate intracellular pathogens which subvert cellular processes to ensure viral replication. Dysregulation of ubiquitination has been implicated in CVB infection. However, how ubiquitination is involved in CVB infection remains unclear. Here we found that the 3D protein of CVB3, the RNA-dependent RNA polymerase, was modified at K220 by K48-linked polyubiquitination which promoted its degradation through proteasome. Proteomic analysis showed that the E3 ligase TRIM56 was upregulated in CVB3-infected cells, while the majority of TRIMs remained unchanged. Pull-down and immunoprecipitation analyses showed that TRIM56 interacted with CVB3 3D. Immunofluorescence observation showed that viral 3D protein was colocalized with TRIM56. TRIM56 overexpression resulted in enhanced ubiquitination of CVB3 3D and decreased virus yield. Moreover, TRIM56 was cleaved by viral 3C protease in CVB3-infected cells. Taken together, this study demonstrated that TRIM56 mediates the ubiquitination and proteasomal degradation of the CVB3 3D protein. These findings demonstrate that TRIM56 is an intrinsic cellular restriction factor against CVB infection, and enhancing viral protein degradation could be a potential strategy to control CVB infection.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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