Cytoplasmic redistribution and cleavage of AUF1 during coxsackievirus infection enhance the stability of its viral genome.

TitleCytoplasmic redistribution and cleavage of AUF1 during coxsackievirus infection enhance the stability of its viral genome.
Publication TypeJournal Article
Year of Publication2013
AuthorsWong, J, Si, X, Angeles, A, Zhang, J, Shi, J, Fung, G, Jagdeo, J, Wang, T, Zhong, Z, Jan, E, Luo, H
JournalFASEB J
Volume27
Issue7
Pagination2777-87
Date Published2013 Jul
ISSN1530-6860
Keywords3' Untranslated Regions, Blotting, Western, Cysteine Endopeptidases, Cytokines, Cytoplasm, Enterovirus B, Human, Gene Expression, Genome, Viral, HeLa Cells, Heterogeneous-Nuclear Ribonucleoprotein D, Host-Pathogen Interactions, Humans, Microscopy, Confocal, Models, Genetic, Oncogene Proteins, Protein Binding, Protein Transport, Proteolysis, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, RNA Stability, RNA, Viral, Viral Proteins, Virus Replication
Abstract

Coxsackievirus B3 (CVB3) is a causative agent of viral myocarditis, hepatitis, pancreatitis, and meningitis in humans. The adenosine-uridine (AU)-rich element RNA binding factor 1 (AUF1) is an integral component in the regulation of gene expression. AUF1 destabilizes mRNAs and targets them for degradation by binding to AU-rich elements in the 3' untranslated region (UTR) of mRNAs. The 3'-UTR of the CVB3 genome contains canonical AU-rich sequences, raising the possibility that CVB3 RNA may also be subjected to AUF1-mediated degradation. Here, we reported that CVB3 infection led to cytoplasmic redistribution and cleavage of AUF1. These events are independent of CVB3-induced caspase activation but require viral protein production. Overexpression of viral protease 2A reproduced CVB3-induced cytoplasmic redistribution of AUF1, while in vitro cleavage assay revealed that viral protease 3C contributed to AUF1 cleavage. Furthermore, we showed that knockdown of AUF1 facilitated viral RNA, protein, and progeny production, suggesting an antiviral property for AUF1 against CVB3 infection. Finally, an immunoprecipitation study demonstrated the physical interaction between AUF1 and the 3'-UTR of CVB3, potentially targeting CVB3 genome toward degradation. Together, our results suggest that cleavage of AUF1 may be a strategy employed by CVB3 to enhance the stability of its viral genome.

DOI10.1096/fj.12-226498
Alternate JournalFASEB J.
PubMed ID23572232
Grant List92214-1 / / Canadian Institutes of Health Research / Canada
97749-1 / / Canadian Institutes of Health Research / Canada
/ / Canadian Institutes of Health Research / Canada