The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication

Abstract Continued outbreaks of Henipaviruses in South Asia and Australia cause severe and lethal disease in both humans and animals. Together, with evidence of human to human transmission for Nipah virus and the lack of preventative or therapeutic measures, its threat to cause a widespread outbreak...

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Autores principales:	Charlene Ranadheera, Roxanne Proulx, Mark Chaiyakul, Shane Jones, Allen Grolla, Anders Leung, John Rutherford, Darwyn Kobasa, Michael Carpenter, Markus Czub
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Nipah Virus (NiV) Henipavirus Viral Genome Production Polymerase Complex Replicase Activity Medicine R Science Q
Acceso en línea:	https://doaj.org/article/348017c0ce1b4717a66427f52b73c64c
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spelling	oai:doaj.org-article:348017c0ce1b4717a66427f52b73c64c2021-12-02T15:08:34ZThe interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication10.1038/s41598-018-34484-72045-2322https://doaj.org/article/348017c0ce1b4717a66427f52b73c64c2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34484-7https://doaj.org/toc/2045-2322Abstract Continued outbreaks of Henipaviruses in South Asia and Australia cause severe and lethal disease in both humans and animals. Together, with evidence of human to human transmission for Nipah virus and the lack of preventative or therapeutic measures, its threat to cause a widespread outbreak and its potential for weaponization has increased. In this study we demonstrate how overexpression of the Nipah virus nucleocapsid protein regulates viral polymerase activity and viral RNA production. By overexpressing the Nipah virus nucleocapsid protein in trans viral transcription was inhibited; however, an increase in viral genome synthesis was observed. Together, the bias of polymerase activity towards genome production led to the severe inhibition of viral progeny. We identified two domains within the nucleocapsid protein, which were each independently capable of binding the viral phosphoprotein. Evident by our data, we propose that the nucleocapsid protein’s ability to interact with the phosphoprotein of the polymerase complex causes a change in polymerase activity and subsequent deficiency in viral replication. This study not only provides insights into the dynamics of Henipavirus RNA synthesis and replication, but also provides insight into potential targets for antiviral drug development.Charlene RanadheeraRoxanne ProulxMark ChaiyakulShane JonesAllen GrollaAnders LeungJohn RutherfordDarwyn KobasaMichael CarpenterMarkus CzubNature PortfolioarticleNipah Virus (NiV)HenipavirusViral Genome ProductionPolymerase ComplexReplicase ActivityMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nipah Virus (NiV) Henipavirus Viral Genome Production Polymerase Complex Replicase Activity Medicine R Science Q
spellingShingle	Nipah Virus (NiV) Henipavirus Viral Genome Production Polymerase Complex Replicase Activity Medicine R Science Q Charlene Ranadheera Roxanne Proulx Mark Chaiyakul Shane Jones Allen Grolla Anders Leung John Rutherford Darwyn Kobasa Michael Carpenter Markus Czub The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
description	Abstract Continued outbreaks of Henipaviruses in South Asia and Australia cause severe and lethal disease in both humans and animals. Together, with evidence of human to human transmission for Nipah virus and the lack of preventative or therapeutic measures, its threat to cause a widespread outbreak and its potential for weaponization has increased. In this study we demonstrate how overexpression of the Nipah virus nucleocapsid protein regulates viral polymerase activity and viral RNA production. By overexpressing the Nipah virus nucleocapsid protein in trans viral transcription was inhibited; however, an increase in viral genome synthesis was observed. Together, the bias of polymerase activity towards genome production led to the severe inhibition of viral progeny. We identified two domains within the nucleocapsid protein, which were each independently capable of binding the viral phosphoprotein. Evident by our data, we propose that the nucleocapsid protein’s ability to interact with the phosphoprotein of the polymerase complex causes a change in polymerase activity and subsequent deficiency in viral replication. This study not only provides insights into the dynamics of Henipavirus RNA synthesis and replication, but also provides insight into potential targets for antiviral drug development.
format	article
author	Charlene Ranadheera Roxanne Proulx Mark Chaiyakul Shane Jones Allen Grolla Anders Leung John Rutherford Darwyn Kobasa Michael Carpenter Markus Czub
author_facet	Charlene Ranadheera Roxanne Proulx Mark Chaiyakul Shane Jones Allen Grolla Anders Leung John Rutherford Darwyn Kobasa Michael Carpenter Markus Czub
author_sort	Charlene Ranadheera
title	The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
title_short	The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
title_full	The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
title_fullStr	The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
title_full_unstemmed	The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
title_sort	interaction between the nipah virus nucleocapsid protein and phosphoprotein regulates virus replication
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/348017c0ce1b4717a66427f52b73c64c
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The interaction between the Nipah virus nucleocapsid protein and phosphoprotein regulates virus replication

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