DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication

ABSTRACT SUMOylation is a reversible posttranslational modification involved in the regulation of diverse biological processes. Growing evidence suggests that virus infection can interfere with the SUMOylation system. In the present study, we discovered that apoptosis inhibitor 5 (API5) is a SUMOyla...

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Autores principales:	Tingjuan Deng, Boli Hu, Xingbo Wang, Yan Yan, Jianwei Zhou, Lulu Lin, Yuting Xu, Xiaojuan Zheng, Jiyong Zhou
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Avibirnavirus VP3 apoptosis inhibitor 5 SUMOylation virus replication IFN-β Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1cc95e1eb4e04c469a0bce0a56666a8e
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spelling	oai:doaj.org-article:1cc95e1eb4e04c469a0bce0a56666a8e2021-11-10T18:37:50ZDeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication10.1128/mBio.01985-212150-7511https://doaj.org/article/1cc95e1eb4e04c469a0bce0a56666a8e2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01985-21https://doaj.org/toc/2150-7511ABSTRACT SUMOylation is a reversible posttranslational modification involved in the regulation of diverse biological processes. Growing evidence suggests that virus infection can interfere with the SUMOylation system. In the present study, we discovered that apoptosis inhibitor 5 (API5) is a SUMOylated protein. Amino acid substitution further identified that Lys404 of API5 was the critical residue for SUMO3 conjugation. Moreover, we found that Avibirnavirus infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. In addition, our results further revealed that viral protein VP3 inhibited the SUMOylation of API5 by targeting API5 and promoting UBC9 proteasome-dependent degradation through binding to the ubiquitin E3 ligase TRAF3. Furthermore, we revealed that wild-type but not K404R mutant API5 inhibited IBDV replication by enhancing MDA5-dependent IFN-β production. Taken together, our data demonstrate that API5 is a UBC9-dependent SUMOylated protein and deSUMOylation of API5 by viral protein VP3 aids in viral replication. IMPORTANCE Apoptosis inhibitor 5 (API5) is a nuclear protein initially identified for its antiapoptotic function. However, so far, posttranslational modification of API5 is unclear. In this study, we first identified that API5 K404 can be conjugated by SUMO3, and Avibirnavirus infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. Mechanically, viral protein VP3 directly interacts with API5 and inhibits SUMOylation of API5. Additionally, the cellular E3 ligase TNF receptor-associated factor 3 (TRAF3) is employed by VP3 to facilitate UBC9 proteasome-dependent degradation, leading to the reduction of API5 SUMOylation. Moreover, our data reveal that SUMOylation of API5 K404 promotes MDA5-dependent beta interferon (IFN-β) induction, and its deSUMOylation contributes to IBDV replication. This work highlights a critical role of conversion between SUMOylation and deSUMOylation of API5 in regulating viral replication.Tingjuan DengBoli HuXingbo WangYan YanJianwei ZhouLulu LinYuting XuXiaojuan ZhengJiyong ZhouAmerican Society for MicrobiologyarticleAvibirnavirus VP3apoptosis inhibitor 5SUMOylationvirus replicationIFN-βMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Avibirnavirus VP3 apoptosis inhibitor 5 SUMOylation virus replication IFN-β Microbiology QR1-502
spellingShingle	Avibirnavirus VP3 apoptosis inhibitor 5 SUMOylation virus replication IFN-β Microbiology QR1-502 Tingjuan Deng Boli Hu Xingbo Wang Yan Yan Jianwei Zhou Lulu Lin Yuting Xu Xiaojuan Zheng Jiyong Zhou DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication
description	ABSTRACT SUMOylation is a reversible posttranslational modification involved in the regulation of diverse biological processes. Growing evidence suggests that virus infection can interfere with the SUMOylation system. In the present study, we discovered that apoptosis inhibitor 5 (API5) is a SUMOylated protein. Amino acid substitution further identified that Lys404 of API5 was the critical residue for SUMO3 conjugation. Moreover, we found that Avibirnavirus infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. In addition, our results further revealed that viral protein VP3 inhibited the SUMOylation of API5 by targeting API5 and promoting UBC9 proteasome-dependent degradation through binding to the ubiquitin E3 ligase TRAF3. Furthermore, we revealed that wild-type but not K404R mutant API5 inhibited IBDV replication by enhancing MDA5-dependent IFN-β production. Taken together, our data demonstrate that API5 is a UBC9-dependent SUMOylated protein and deSUMOylation of API5 by viral protein VP3 aids in viral replication. IMPORTANCE Apoptosis inhibitor 5 (API5) is a nuclear protein initially identified for its antiapoptotic function. However, so far, posttranslational modification of API5 is unclear. In this study, we first identified that API5 K404 can be conjugated by SUMO3, and Avibirnavirus infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. Mechanically, viral protein VP3 directly interacts with API5 and inhibits SUMOylation of API5. Additionally, the cellular E3 ligase TNF receptor-associated factor 3 (TRAF3) is employed by VP3 to facilitate UBC9 proteasome-dependent degradation, leading to the reduction of API5 SUMOylation. Moreover, our data reveal that SUMOylation of API5 K404 promotes MDA5-dependent beta interferon (IFN-β) induction, and its deSUMOylation contributes to IBDV replication. This work highlights a critical role of conversion between SUMOylation and deSUMOylation of API5 in regulating viral replication.
format	article
author	Tingjuan Deng Boli Hu Xingbo Wang Yan Yan Jianwei Zhou Lulu Lin Yuting Xu Xiaojuan Zheng Jiyong Zhou
author_facet	Tingjuan Deng Boli Hu Xingbo Wang Yan Yan Jianwei Zhou Lulu Lin Yuting Xu Xiaojuan Zheng Jiyong Zhou
author_sort	Tingjuan Deng
title	DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication
title_short	DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication
title_full	DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication
title_fullStr	DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication
title_full_unstemmed	DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication
title_sort	desumoylation of apoptosis inhibitor 5 by <italic toggle="yes">avibirnavirus</italic> vp3 supports virus replication
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/1cc95e1eb4e04c469a0bce0a56666a8e
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DeSUMOylation of Apoptosis Inhibitor 5 by <italic toggle="yes">Avibirnavirus</italic> VP3 Supports Virus Replication

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