EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.

Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict vir...

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Autores principales:	Kevin Tsai, Nadezhda Thikmyanova, Jason A Wojcechowskyj, Henri-Jacques Delecluse, Paul M Lieberman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3621579e6a134f919202e24efd4386eb
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spelling	oai:doaj.org-article:3621579e6a134f919202e24efd4386eb2021-11-18T06:05:08ZEBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.1553-73661553-737410.1371/journal.ppat.1002376https://doaj.org/article/3621579e6a134f919202e24efd4386eb2011-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22102817/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus.Kevin TsaiNadezhda ThikmyanovaJason A WojcechowskyjHenri-Jacques DeleclusePaul M LiebermanPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 11, p e1002376 (2011)
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 Kevin Tsai Nadezhda Thikmyanova Jason A Wojcechowskyj Henri-Jacques Delecluse Paul M Lieberman EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
description	Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus.
format	article
author	Kevin Tsai Nadezhda Thikmyanova Jason A Wojcechowskyj Henri-Jacques Delecluse Paul M Lieberman
author_facet	Kevin Tsai Nadezhda Thikmyanova Jason A Wojcechowskyj Henri-Jacques Delecluse Paul M Lieberman
author_sort	Kevin Tsai
title	EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
title_short	EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
title_full	EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
title_fullStr	EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
title_full_unstemmed	EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
title_sort	ebv tegument protein bnrf1 disrupts daxx-atrx to activate viral early gene transcription.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3621579e6a134f919202e24efd4386eb
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EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.

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