Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.

The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV...

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Autores principales:	Stefano Gastaldello, Xinsong Chen, Simone Callegari, Maria G Masucci
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/55d18d0a347146babdef97ee65cd53de
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spelling	oai:doaj.org-article:55d18d0a347146babdef97ee65cd53de2021-11-18T06:07:31ZCaspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.1553-73661553-737410.1371/journal.ppat.1003664https://doaj.org/article/55d18d0a347146babdef97ee65cd53de2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24130483/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication.Stefano GastaldelloXinsong ChenSimone CallegariMaria G MasucciPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003664 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Stefano Gastaldello Xinsong Chen Simone Callegari Maria G Masucci Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
description	The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication.
format	article
author	Stefano Gastaldello Xinsong Chen Simone Callegari Maria G Masucci
author_facet	Stefano Gastaldello Xinsong Chen Simone Callegari Maria G Masucci
author_sort	Stefano Gastaldello
title	Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
title_short	Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
title_full	Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
title_fullStr	Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
title_full_unstemmed	Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
title_sort	caspase-1 promotes epstein-barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/55d18d0a347146babdef97ee65cd53de
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Caspase-1 promotes Epstein-Barr virus replication by targeting the large tegument protein deneddylase to the nucleus of productively infected cells.

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