[HTML][HTML] Early growth response gene-1 suppresses foot-and-mouth disease virus replication by enhancing type I interferon pathway signal transduction

Z Zhu, X Du, F Yang, H Zheng - Frontiers in Microbiology, 2018 - frontiersin.org
Z Zhu, X Du, F Yang, H Zheng
Frontiers in Microbiology, 2018frontiersin.org
Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is
implicated in viral infection. In this study, we observed that foot-and-mouth disease virus
(FMDV) infection significantly triggered EGR1 expression. Overexpression of EGR1
suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably
promoted FMDV replication. A previously reported FMDV mutant virus (with two amino acids
mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was …
Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is implicated in viral infection. In this study, we observed that foot-and-mouth disease virus (FMDV) infection significantly triggered EGR1 expression. Overexpression of EGR1 suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably promoted FMDV replication. A previously reported FMDV mutant virus (with two amino acids mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was used in this study. We found that SAP mutant FMDV infection induced a higher expression of EGR1 than wildtype FMDV infection, and also triggered higher IFN-β and IFN-stimulated genes (ISGs) expression than wildtype FMDV infection. This implied a link between EGR1 and type I IFN signaling. Further study showed that overexpression of EGR1 resulted in Sendai virus (SeV)-induced IFN-stimulated response element (ISRE) and NF-κB promoter activation. In addition, the SeV-induced ISGs expression was impaired in EGR1 knockdown cells. EGR1 upregulation promoted type I IFN signaling activation and suppressed FMDV and Seneca Valley virus replication. Suppression of the transcriptional activity of EGR1 did not affect its antiviral effect against FMDV. This study reveals a new mechanism evolved by EGR1 to enhance type I IFN signaling and suppress FMDV replication.
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