Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.

The human papillomavirus (HPV) vaccines effectively protect against new infections of up to four HPV subtypes. However, these vaccines are not protective against many other clinically relevant HPV subtypes and are ineffective at treating established HPV infections. There is therefore a significant n...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Christine M Helfer, Ranran Wang, Jianxin You
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae021cb1bfa24b26abcf5492f75902a4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ae021cb1bfa24b26abcf5492f75902a4
record_format	dspace
spelling	oai:doaj.org-article:ae021cb1bfa24b26abcf5492f75902a42021-11-18T08:49:24ZAnalysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.1932-620310.1371/journal.pone.0077994https://doaj.org/article/ae021cb1bfa24b26abcf5492f75902a42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24205059/?tool=EBIhttps://doaj.org/toc/1932-6203The human papillomavirus (HPV) vaccines effectively protect against new infections of up to four HPV subtypes. However, these vaccines are not protective against many other clinically relevant HPV subtypes and are ineffective at treating established HPV infections. There is therefore a significant need for antiviral treatments for persistent HPV infections. A promising anti-HPV drug target is the interaction between the HPV E2 protein and cellular bromodomain-containing protein 4 (Brd4) since this protein complex mediates several processes important for the viral life cycle including viral genome maintenance, replication, and transcription. Using bimolecular fluorescence complementation (BiFC) technology, we demonstrate the E2 and Brd4 interaction on both interphase chromatin and mitotic chromosomes throughout mitosis. The E2-Brd4 BiFC was significantly diminished by mutating the Brd4 binding sites in E2 or by a dominant negative inhibitor of the E2-Brd4 interaction, demonstrating the potential of BiFC for identifying inhibitors of this important virus-host interaction. Importantly, when Brd4 was released from chromatin using the bromodomain inhibitor JQ1(+), the E2-Brd4 interacting complex relocated into foci that no longer associate with mitotic chromosomes, pointing to JQ1(+) as a promising antiviral inhibitor of HPV genome maintenance during HPV persistent infection.Christine M HelferRanran WangJianxin YouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e77994 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christine M Helfer Ranran Wang Jianxin You Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.
description	The human papillomavirus (HPV) vaccines effectively protect against new infections of up to four HPV subtypes. However, these vaccines are not protective against many other clinically relevant HPV subtypes and are ineffective at treating established HPV infections. There is therefore a significant need for antiviral treatments for persistent HPV infections. A promising anti-HPV drug target is the interaction between the HPV E2 protein and cellular bromodomain-containing protein 4 (Brd4) since this protein complex mediates several processes important for the viral life cycle including viral genome maintenance, replication, and transcription. Using bimolecular fluorescence complementation (BiFC) technology, we demonstrate the E2 and Brd4 interaction on both interphase chromatin and mitotic chromosomes throughout mitosis. The E2-Brd4 BiFC was significantly diminished by mutating the Brd4 binding sites in E2 or by a dominant negative inhibitor of the E2-Brd4 interaction, demonstrating the potential of BiFC for identifying inhibitors of this important virus-host interaction. Importantly, when Brd4 was released from chromatin using the bromodomain inhibitor JQ1(+), the E2-Brd4 interacting complex relocated into foci that no longer associate with mitotic chromosomes, pointing to JQ1(+) as a promising antiviral inhibitor of HPV genome maintenance during HPV persistent infection.
format	article
author	Christine M Helfer Ranran Wang Jianxin You
author_facet	Christine M Helfer Ranran Wang Jianxin You
author_sort	Christine M Helfer
title	Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.
title_short	Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.
title_full	Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.
title_fullStr	Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.
title_full_unstemmed	Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.
title_sort	analysis of the papillomavirus e2 and bromodomain protein brd4 interaction using bimolecular fluorescence complementation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ae021cb1bfa24b26abcf5492f75902a4
work_keys_str_mv	AT christinemhelfer analysisofthepapillomaviruse2andbromodomainproteinbrd4interactionusingbimolecularfluorescencecomplementation AT ranranwang analysisofthepapillomaviruse2andbromodomainproteinbrd4interactionusingbimolecularfluorescencecomplementation AT jianxinyou analysisofthepapillomaviruse2andbromodomainproteinbrd4interactionusingbimolecularfluorescencecomplementation
_version_	1718421281632681984

Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.

Ejemplares similares