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TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation

Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3–6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation o...

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Autores principales: Wang, Suyan, Yu, Mengmeng, Liu, Aijing, Bao, Yuanling, Qi, Xiaole, Gao, Li, Chen, Yuntong, Liu, Peng, Wang, Yulong, Xing, Lixiao, Meng, Lingzhai, Zhang, Yu, Fan, Linjin, Li, Xinyi, Pan, Qing, Zhang, Yanping, Cui, Hongyu, Li, Kai, Liu, Changjun, He, Xijun, Gao, Yulong, Wang, Xiaomei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459960/
https://www.ncbi.nlm.nih.gov/pubmed/34516573
http://dx.doi.org/10.1371/journal.ppat.1009900
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author Wang, Suyan
Yu, Mengmeng
Liu, Aijing
Bao, Yuanling
Qi, Xiaole
Gao, Li
Chen, Yuntong
Liu, Peng
Wang, Yulong
Xing, Lixiao
Meng, Lingzhai
Zhang, Yu
Fan, Linjin
Li, Xinyi
Pan, Qing
Zhang, Yanping
Cui, Hongyu
Li, Kai
Liu, Changjun
He, Xijun
Gao, Yulong
Wang, Xiaomei
author_facet Wang, Suyan
Yu, Mengmeng
Liu, Aijing
Bao, Yuanling
Qi, Xiaole
Gao, Li
Chen, Yuntong
Liu, Peng
Wang, Yulong
Xing, Lixiao
Meng, Lingzhai
Zhang, Yu
Fan, Linjin
Li, Xinyi
Pan, Qing
Zhang, Yanping
Cui, Hongyu
Li, Kai
Liu, Changjun
He, Xijun
Gao, Yulong
Wang, Xiaomei
author_sort Wang, Suyan
collection PubMed
description Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3–6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation of antiviral effectors to restrict viral replication. Here, we conducted RNA-seq in avian cells infected by IBDV and identified TRIM25 as a host restriction factor. Specifically, TRIM25 deficiency dramatically increased viral yields, whereas overexpression of TRIM25 significantly inhibited IBDV replication. Immunoprecipitation assays indicated that TRIM25 only interacted with VP3 among all viral proteins, mediating its K27-linked polyubiquitination and subsequent proteasomal degradation. Moreover, the Lys854 residue of VP3 was identified as the key target site for the ubiquitination catalyzed by TRIM25. The ubiquitination site destroyed enhanced the replication ability of IBDV in vitro and in vivo. These findings demonstrated that TRIM25 inhibited IBDV replication by specifically ubiquitinating and degrading the structural protein VP3.
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spelling pubmed-84599602021-09-24 TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation Wang, Suyan Yu, Mengmeng Liu, Aijing Bao, Yuanling Qi, Xiaole Gao, Li Chen, Yuntong Liu, Peng Wang, Yulong Xing, Lixiao Meng, Lingzhai Zhang, Yu Fan, Linjin Li, Xinyi Pan, Qing Zhang, Yanping Cui, Hongyu Li, Kai Liu, Changjun He, Xijun Gao, Yulong Wang, Xiaomei PLoS Pathog Research Article Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3–6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation of antiviral effectors to restrict viral replication. Here, we conducted RNA-seq in avian cells infected by IBDV and identified TRIM25 as a host restriction factor. Specifically, TRIM25 deficiency dramatically increased viral yields, whereas overexpression of TRIM25 significantly inhibited IBDV replication. Immunoprecipitation assays indicated that TRIM25 only interacted with VP3 among all viral proteins, mediating its K27-linked polyubiquitination and subsequent proteasomal degradation. Moreover, the Lys854 residue of VP3 was identified as the key target site for the ubiquitination catalyzed by TRIM25. The ubiquitination site destroyed enhanced the replication ability of IBDV in vitro and in vivo. These findings demonstrated that TRIM25 inhibited IBDV replication by specifically ubiquitinating and degrading the structural protein VP3. Public Library of Science 2021-09-13 /pmc/articles/PMC8459960/ /pubmed/34516573 http://dx.doi.org/10.1371/journal.ppat.1009900 Text en © 2021 Wang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Suyan
Yu, Mengmeng
Liu, Aijing
Bao, Yuanling
Qi, Xiaole
Gao, Li
Chen, Yuntong
Liu, Peng
Wang, Yulong
Xing, Lixiao
Meng, Lingzhai
Zhang, Yu
Fan, Linjin
Li, Xinyi
Pan, Qing
Zhang, Yanping
Cui, Hongyu
Li, Kai
Liu, Changjun
He, Xijun
Gao, Yulong
Wang, Xiaomei
TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation
title TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation
title_full TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation
title_fullStr TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation
title_full_unstemmed TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation
title_short TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation
title_sort trim25 inhibits infectious bursal disease virus replication by targeting vp3 for ubiquitination and degradation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459960/
https://www.ncbi.nlm.nih.gov/pubmed/34516573
http://dx.doi.org/10.1371/journal.ppat.1009900
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