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2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21

Senecavirus A (SVA), also known as Seneca Valley virus, is a recently discovered picornavirus that can cause swine vesicular disease, posing a great threat to the global swine industry. It can replicate efficiently in cells, but the molecular mechanism remains poorly understood. This study determine...

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Autores principales: Zhao, Kuan, Guo, Xiao-Ran, Liu, Shuai-Feng, Liu, Xiao-Na, Han, Ying, Wang, Lu-Lu, Lei, Bai-Shi, Zhang, Wu-Chao, Li, Li-Min, Yuan, Wan-Zhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329633/
https://www.ncbi.nlm.nih.gov/pubmed/35911774
http://dx.doi.org/10.3389/fimmu.2022.951984
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author Zhao, Kuan
Guo, Xiao-Ran
Liu, Shuai-Feng
Liu, Xiao-Na
Han, Ying
Wang, Lu-Lu
Lei, Bai-Shi
Zhang, Wu-Chao
Li, Li-Min
Yuan, Wan-Zhe
author_facet Zhao, Kuan
Guo, Xiao-Ran
Liu, Shuai-Feng
Liu, Xiao-Na
Han, Ying
Wang, Lu-Lu
Lei, Bai-Shi
Zhang, Wu-Chao
Li, Li-Min
Yuan, Wan-Zhe
author_sort Zhao, Kuan
collection PubMed
description Senecavirus A (SVA), also known as Seneca Valley virus, is a recently discovered picornavirus that can cause swine vesicular disease, posing a great threat to the global swine industry. It can replicate efficiently in cells, but the molecular mechanism remains poorly understood. This study determined the host’s differentially expressed proteins (DEPs) during SVA infection using dimethyl labeling based on quantitative proteomics. Among the DE proteins, DDX21, a member of the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase (DDX) family, was downregulated and demonstrated inhibiting SVA replication by overexpression and knockdown experiment. To antagonize this antiviral effect of DDX21, SVA infection induces the degradation of DDX21 by 2B and 3C proteins. The Co-IP results showed that 2B and 3C did not interact with DDX21, suggesting that the degradation of DDX21 did not depend on their interaction. Moreover, the 3C protein protease activity was necessary for the degradation of DDX21. Furthermore, our study revealed that the degradation of DDX21 by 2B and 3C proteins of SVA was achieved through the caspase pathway. These findings suggest that DDX21 was an effective antiviral factor for suppressing SVA infection and that SVA antagonized its antiviral effect by degrading DDX21, which will be useful to guide further studies into the mechanism of mutual regulation between SVA and the host.
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spelling pubmed-93296332022-07-29 2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21 Zhao, Kuan Guo, Xiao-Ran Liu, Shuai-Feng Liu, Xiao-Na Han, Ying Wang, Lu-Lu Lei, Bai-Shi Zhang, Wu-Chao Li, Li-Min Yuan, Wan-Zhe Front Immunol Immunology Senecavirus A (SVA), also known as Seneca Valley virus, is a recently discovered picornavirus that can cause swine vesicular disease, posing a great threat to the global swine industry. It can replicate efficiently in cells, but the molecular mechanism remains poorly understood. This study determined the host’s differentially expressed proteins (DEPs) during SVA infection using dimethyl labeling based on quantitative proteomics. Among the DE proteins, DDX21, a member of the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase (DDX) family, was downregulated and demonstrated inhibiting SVA replication by overexpression and knockdown experiment. To antagonize this antiviral effect of DDX21, SVA infection induces the degradation of DDX21 by 2B and 3C proteins. The Co-IP results showed that 2B and 3C did not interact with DDX21, suggesting that the degradation of DDX21 did not depend on their interaction. Moreover, the 3C protein protease activity was necessary for the degradation of DDX21. Furthermore, our study revealed that the degradation of DDX21 by 2B and 3C proteins of SVA was achieved through the caspase pathway. These findings suggest that DDX21 was an effective antiviral factor for suppressing SVA infection and that SVA antagonized its antiviral effect by degrading DDX21, which will be useful to guide further studies into the mechanism of mutual regulation between SVA and the host. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9329633/ /pubmed/35911774 http://dx.doi.org/10.3389/fimmu.2022.951984 Text en Copyright © 2022 Zhao, Guo, Liu, Liu, Han, Wang, Lei, Zhang, Li and Yuan 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
Zhao, Kuan
Guo, Xiao-Ran
Liu, Shuai-Feng
Liu, Xiao-Na
Han, Ying
Wang, Lu-Lu
Lei, Bai-Shi
Zhang, Wu-Chao
Li, Li-Min
Yuan, Wan-Zhe
2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
title 2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
title_full 2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
title_fullStr 2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
title_full_unstemmed 2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
title_short 2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
title_sort 2b and 3c proteins of senecavirus a antagonize the antiviral activity of ddx21 via the caspase-dependent degradation of ddx21
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329633/
https://www.ncbi.nlm.nih.gov/pubmed/35911774
http://dx.doi.org/10.3389/fimmu.2022.951984
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