Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction.

Zixiang Zhu,Fan Yang,Hong Tian,Xiangtao Liu,Pengfei Li,Haixue Zheng,Keshan Zhang,Xiangle Zhang,Weijun Cao,Xiaoli Du

doi:10.3389/fmicb.2018.02326

Abstract

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.

Highlights

Foot-and-mouth disease virus (FMDV) is a non-enveloped virus with positive-sense and singlestranded RNA genome
Transcripts of Early growth response gene-1 (EGR1) were considerably upregulated after foot-and-mouth disease virus (FMDV) infection and reached to the highest level at 8 hpi
This indicated that EGR1 expression was not induced by IFNβ treatment; FMDV infection could induce EGR1 expression

Summary

Introduction

Foot-and-mouth disease virus (FMDV) is a non-enveloped virus with positive-sense and singlestranded RNA genome. The viral genome is approximately 8.5 kb nucleotides in length, including a single large open reading frame that encodes a polyprotein. EGR1 Suppresses FMDV Replication responses, cause immunosuppression, and promote viral replication and infection (Mason et al, 2003; Rodriguez Pulido and Saiz, 2017). FMDV causes an acute vesicular disease of infected animals, which is called foot-and-mouth disease (FMD). The understanding of host-FMDV interaction as well as the involved mechanism contributes to the planning of new strategies for FMD prevention (Domingo et al, 2005; Rweyemamu et al, 2008b; Rodriguez Pulido and Saiz, 2017). Many researches on host responses in FMDV-infected cells have to be investigated

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Conclusion