The DDX23 Negatively Regulates Translation and Replication of Foot-and-Mouth Disease Virus and Is Degraded by 3C Proteinase
Open Access
- 24 November 2020
- Vol. 12 (12), 1348
- https://doi.org/10.3390/v12121348
Abstract
DEAD-box helicase 23 (DDX23) is a host nuclear helicase, which is a part of the spliceosomal complex and involved in pre-mRNA splicing. To investigate whether DDX23, an internal ribosomal entry sites transacting factor (ITAF) affects foot-and-mouth disease virus (FMDV) replication and translation through internal ribosome entry site (IRES)-dependent manner. For this, we utilized a pull-down assay, Western blotting, quantitative real-time PCR, confocal microscopy, overexpression and small interfering RNA knockdown, as well as the median tissue culture infective dose. Our findings showed that FMDV infection inhibited DDX23 expression and the overexpression of DDX23 reduced viral replication, however, CRISPR Cas9 knockout/small interfering RNA knockdown increased FMDV replication. FMDV IRES domain III and IV interacted with DDX23, whereas DDX23 interacted with FMDV 3C proteinase and significantly degraded. The enzymatic activity of FMDV 3C proteinase degraded DDX23, whereas FMDV degraded DDX23 via the lysosomal pathway. Additionally, IRES-driven translation was suppressed in DDX23-overexpressing cells, and was enhanced in DDX23 knocked down. Collectively, our results demonstrated that DDX23 negatively affects FMDV IRES-dependent translation, which could be a useful target for the design of antiviral drugs.This publication has 71 references indexed in Scilit:
- Foot-and-Mouth Disease Virus 3C Protease Cleaves NEMO To Impair Innate Immune SignalingJournal of Virology, 2012
- Attenuation of 40S Ribosomal Subunit Abundance Differentially Affects Host and HCV Translation and Suppresses HCV ReplicationPLoS Pathogens, 2012
- From unwinding to clamping — the DEAD box RNA helicase familyNature Reviews Molecular Cell Biology, 2011
- RIG-I-Mediated Antiviral Signaling Is Inhibited in HIV-1 Infection by a Protease-Mediated Sequestration of RIG-IJournal of Virology, 2011
- RNA helicasesRNA Biology, 2010
- Recognition of viruses by cytoplasmic sensorsCurrent Opinion in Immunology, 2010
- A novel role for Gemin5 in mRNA translationNucleic Acids Research, 2008
- Structural insights into the transcriptional and translational roles of Ebp1The EMBO Journal, 2007
- Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot-and-mouth disease virus RNARNA, 2007
- The DEAD-box protein family of RNA helicasesGene, 2006