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

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 ce...

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Autores principales: Zhu, Zixiang, Du, Xiaoli, Li, Pengfei, Zhang, Xiangle, Yang, Fan, Cao, Weijun, Tian, Hong, Zhang, Keshan, Liu, Xiangtao, Zheng, Haixue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170816/
https://www.ncbi.nlm.nih.gov/pubmed/30319594
http://dx.doi.org/10.3389/fmicb.2018.02326
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author Zhu, Zixiang
Du, Xiaoli
Li, Pengfei
Zhang, Xiangle
Yang, Fan
Cao, Weijun
Tian, Hong
Zhang, Keshan
Liu, Xiangtao
Zheng, Haixue
author_facet Zhu, Zixiang
Du, Xiaoli
Li, Pengfei
Zhang, Xiangle
Yang, Fan
Cao, Weijun
Tian, Hong
Zhang, Keshan
Liu, Xiangtao
Zheng, Haixue
author_sort Zhu, Zixiang
collection PubMed
description 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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spelling pubmed-61708162018-10-12 Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction Zhu, Zixiang Du, Xiaoli Li, Pengfei Zhang, Xiangle Yang, Fan Cao, Weijun Tian, Hong Zhang, Keshan Liu, Xiangtao Zheng, Haixue Front Microbiol Microbiology 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. Frontiers Media S.A. 2018-09-27 /pmc/articles/PMC6170816/ /pubmed/30319594 http://dx.doi.org/10.3389/fmicb.2018.02326 Text en Copyright © 2018 Zhu, Du, Li, Zhang, Yang, Cao, Tian, Zhang, Liu and Zheng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhu, Zixiang
Du, Xiaoli
Li, Pengfei
Zhang, Xiangle
Yang, Fan
Cao, Weijun
Tian, Hong
Zhang, Keshan
Liu, Xiangtao
Zheng, Haixue
Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction
title Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction
title_full Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction
title_fullStr Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction
title_full_unstemmed Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction
title_short Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction
title_sort early growth response gene-1 suppresses foot-and-mouth disease virus replication by enhancing type i interferon pathway signal transduction
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170816/
https://www.ncbi.nlm.nih.gov/pubmed/30319594
http://dx.doi.org/10.3389/fmicb.2018.02326
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