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Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication
The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 sup...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477588/ https://www.ncbi.nlm.nih.gov/pubmed/28406479 http://dx.doi.org/10.1038/cddis.2017.170 |
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author | Zhu, Zixiang Li, Chuntian Du, Xiaoli Wang, Guoqing Cao, Weijun Yang, Fan Feng, Huanhuan Zhang, Xiangle Shi, Zhengwang Liu, Huanan Tian, Hong Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue |
author_facet | Zhu, Zixiang Li, Chuntian Du, Xiaoli Wang, Guoqing Cao, Weijun Yang, Fan Feng, Huanhuan Zhang, Xiangle Shi, Zhengwang Liu, Huanan Tian, Hong Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue |
author_sort | Zhu, Zixiang |
collection | PubMed |
description | The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 suppressed FMDV replication, and the inflammatory response was significantly inhibited by LGP2 in virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV. Disruption of RNA recognition by LGP2 is suggested to abolish completely LGP2-mediated antiviral activity against FMDV. FMDV leader protein (L(pro)), as well as the 3C(pro) and 2B proteins were determined to possess the ability to induce reduction of LGP2 protein expression. 2B-induced reduction of LGP2 was independent of cleavage of eukaryotic translation initiation factor 4 gamma; and the proteasomes, lysosomes or caspase-dependent pathways were not involved in this process. The C-terminal amino acids of 101–154 were essential for 2B-induced reduction of LGP2 and upregulation of inflammatory response. Direct interaction was demonstrated between LGP2 and 2B. Our results describe the antiviral role of LGP2 against FMDV and a novel antagonistic mechanism of FMDV that is mediated by 2B protein. |
format | Online Article Text |
id | pubmed-5477588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54775882017-07-03 Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication Zhu, Zixiang Li, Chuntian Du, Xiaoli Wang, Guoqing Cao, Weijun Yang, Fan Feng, Huanhuan Zhang, Xiangle Shi, Zhengwang Liu, Huanan Tian, Hong Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue Cell Death Dis Original Article The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 suppressed FMDV replication, and the inflammatory response was significantly inhibited by LGP2 in virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV. Disruption of RNA recognition by LGP2 is suggested to abolish completely LGP2-mediated antiviral activity against FMDV. FMDV leader protein (L(pro)), as well as the 3C(pro) and 2B proteins were determined to possess the ability to induce reduction of LGP2 protein expression. 2B-induced reduction of LGP2 was independent of cleavage of eukaryotic translation initiation factor 4 gamma; and the proteasomes, lysosomes or caspase-dependent pathways were not involved in this process. The C-terminal amino acids of 101–154 were essential for 2B-induced reduction of LGP2 and upregulation of inflammatory response. Direct interaction was demonstrated between LGP2 and 2B. Our results describe the antiviral role of LGP2 against FMDV and a novel antagonistic mechanism of FMDV that is mediated by 2B protein. Nature Publishing Group 2017-04 2017-04-13 /pmc/articles/PMC5477588/ /pubmed/28406479 http://dx.doi.org/10.1038/cddis.2017.170 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Zhu, Zixiang Li, Chuntian Du, Xiaoli Wang, Guoqing Cao, Weijun Yang, Fan Feng, Huanhuan Zhang, Xiangle Shi, Zhengwang Liu, Huanan Tian, Hong Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication |
title | Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication |
title_full | Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication |
title_fullStr | Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication |
title_full_unstemmed | Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication |
title_short | Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication |
title_sort | foot-and-mouth disease virus infection inhibits lgp2 protein expression to exaggerate inflammatory response and promote viral replication |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477588/ https://www.ncbi.nlm.nih.gov/pubmed/28406479 http://dx.doi.org/10.1038/cddis.2017.170 |
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