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Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication

Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of cloven-hoofed animals. In order to establish an infection, the FMD virus (FMDV) needs to counteract host antiviral responses. Tumor progression locus 2 (TPL2), a mitogen-activated protein kinase, can regulate innate and ada...

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Autores principales: Hao, Junhong, Shen, Chaochao, Wei, Nannan, Yan, Minghao, Zhang, Xuegang, Xu, Guowei, Zhang, Dajun, Hou, Jing, Cao, Weijun, Jin, Ye, Zhang, Keshan, Zheng, Haixue, Liu, Xiangtao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821752/
https://www.ncbi.nlm.nih.gov/pubmed/33488582
http://dx.doi.org/10.3389/fimmu.2020.580334
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author Hao, Junhong
Shen, Chaochao
Wei, Nannan
Yan, Minghao
Zhang, Xuegang
Xu, Guowei
Zhang, Dajun
Hou, Jing
Cao, Weijun
Jin, Ye
Zhang, Keshan
Zheng, Haixue
Liu, Xiangtao
author_facet Hao, Junhong
Shen, Chaochao
Wei, Nannan
Yan, Minghao
Zhang, Xuegang
Xu, Guowei
Zhang, Dajun
Hou, Jing
Cao, Weijun
Jin, Ye
Zhang, Keshan
Zheng, Haixue
Liu, Xiangtao
author_sort Hao, Junhong
collection PubMed
description Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of cloven-hoofed animals. In order to establish an infection, the FMD virus (FMDV) needs to counteract host antiviral responses. Tumor progression locus 2 (TPL2), a mitogen-activated protein kinase, can regulate innate and adaptive immunity; however, its exact mechanisms underlying TPL2-mediated regulation of the pathogenesis of FMDV infection remain unknown. In this study, we confirmed that TPL2 could inhibit FMDV replication in vitro and in vivo. The virus replication increased in Tpl2-deficient suckling mice in association with reduced expression of interferon-stimulated genes interferon-α (IFN-α) and myxovirus resistance (MX2) and significantly reduced expression of C-X-C motif chemokine ligand 10 (CXCL10), interferon regulatory factor 3 (IRF3), and IRF7, while the phosphorylation of IRF3 was not detected. Moreover, the interactions between TPL2 and VP1 were also confirmed. The overexpression of TPL2 promoted IRF3-mediated dose-dependent activation of the IFN-β signaling pathway in association with interactions between IRF3 and TPL2. VP1 also inhibited phosphorylation of TPL2 at Thr290, while Thr290 resulted as the key functional site associated with the TPL2-mediated antiviral response. Taken together, this study indicated that FMDV capsid protein VP1 antagonizes TPL2-mediated activation of the IRF3/IFN-β signaling pathway for immune escape and facilitated virus replication.
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spelling pubmed-78217522021-01-23 Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication Hao, Junhong Shen, Chaochao Wei, Nannan Yan, Minghao Zhang, Xuegang Xu, Guowei Zhang, Dajun Hou, Jing Cao, Weijun Jin, Ye Zhang, Keshan Zheng, Haixue Liu, Xiangtao Front Immunol Immunology Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of cloven-hoofed animals. In order to establish an infection, the FMD virus (FMDV) needs to counteract host antiviral responses. Tumor progression locus 2 (TPL2), a mitogen-activated protein kinase, can regulate innate and adaptive immunity; however, its exact mechanisms underlying TPL2-mediated regulation of the pathogenesis of FMDV infection remain unknown. In this study, we confirmed that TPL2 could inhibit FMDV replication in vitro and in vivo. The virus replication increased in Tpl2-deficient suckling mice in association with reduced expression of interferon-stimulated genes interferon-α (IFN-α) and myxovirus resistance (MX2) and significantly reduced expression of C-X-C motif chemokine ligand 10 (CXCL10), interferon regulatory factor 3 (IRF3), and IRF7, while the phosphorylation of IRF3 was not detected. Moreover, the interactions between TPL2 and VP1 were also confirmed. The overexpression of TPL2 promoted IRF3-mediated dose-dependent activation of the IFN-β signaling pathway in association with interactions between IRF3 and TPL2. VP1 also inhibited phosphorylation of TPL2 at Thr290, while Thr290 resulted as the key functional site associated with the TPL2-mediated antiviral response. Taken together, this study indicated that FMDV capsid protein VP1 antagonizes TPL2-mediated activation of the IRF3/IFN-β signaling pathway for immune escape and facilitated virus replication. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7821752/ /pubmed/33488582 http://dx.doi.org/10.3389/fimmu.2020.580334 Text en Copyright © 2021 Hao, Shen, Wei, Yan, Zhang, Xu, Zhang, Hou, Cao, Jin, Zhang, Zheng and Liu https://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 Immunology
Hao, Junhong
Shen, Chaochao
Wei, Nannan
Yan, Minghao
Zhang, Xuegang
Xu, Guowei
Zhang, Dajun
Hou, Jing
Cao, Weijun
Jin, Ye
Zhang, Keshan
Zheng, Haixue
Liu, Xiangtao
Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication
title Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication
title_full Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication
title_fullStr Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication
title_full_unstemmed Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication
title_short Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication
title_sort foot-and-mouth disease virus capsid protein vp1 antagonizes tpl2-mediated activation of the irf3/ifn-β signaling pathway to facilitate the virus replication
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821752/
https://www.ncbi.nlm.nih.gov/pubmed/33488582
http://dx.doi.org/10.3389/fimmu.2020.580334
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