A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.

The mechanism regulating expression of late genes, encoding viral structural components, is an unresolved problem in the biology of DNA tumor viruses. Here we show that BGLF4, the only protein kinase encoded by Epstein-Barr virus (EBV), controls expression of late genes independent of its effect on...

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Autores principales:	Ayman El-Guindy, Francesc Lopez-Giraldez, Henri-Jacques Delecluse, Jessica McKenzie, George Miller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/962dfcb570484e159f9575acb51accf5
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spelling	oai:doaj.org-article:962dfcb570484e159f9575acb51accf52021-11-25T05:46:07ZA locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.1553-73661553-737410.1371/journal.ppat.1004307https://doaj.org/article/962dfcb570484e159f9575acb51accf52014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25166506/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The mechanism regulating expression of late genes, encoding viral structural components, is an unresolved problem in the biology of DNA tumor viruses. Here we show that BGLF4, the only protein kinase encoded by Epstein-Barr virus (EBV), controls expression of late genes independent of its effect on viral DNA replication. Ectopic expression of BGLF4 in cells lacking the kinase gene stimulated the transcript levels of six late genes by 8- to 10-fold. Introduction of a BGLF4 mutant that eliminated its kinase activity did not stimulate late gene expression. In cells infected with wild-type EBV, siRNA to BGLF4 (siG4) markedly reduced late gene expression without compromising viral DNA replication. Synthesis of late products was restored upon expression of a form of BGLF4 resistant to the siRNA. Studying the EBV transcriptome using mRNA-seq during the late phase of the lytic cycle in the absence and presence of siG4 showed that BGLF4 controlled expression of 31 late genes. Analysis of the EBV transcriptome identified BGLF3 as a gene whose expression was reduced as a result of silencing BGLF4. Knockdown of BGLF3 markedly reduced late gene expression but had no effect on viral DNA replication or expression of BGLF4. Our findings reveal the presence of a late control locus encompassing BGLF3 and BGLF4 in the EBV genome, and provide evidence for the importance of both proteins in post-replication events that are necessary for expression of late genes.Ayman El-GuindyFrancesc Lopez-GiraldezHenri-Jacques DelecluseJessica McKenzieGeorge MillerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 8, p e1004307 (2014)
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 Ayman El-Guindy Francesc Lopez-Giraldez Henri-Jacques Delecluse Jessica McKenzie George Miller A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
description	The mechanism regulating expression of late genes, encoding viral structural components, is an unresolved problem in the biology of DNA tumor viruses. Here we show that BGLF4, the only protein kinase encoded by Epstein-Barr virus (EBV), controls expression of late genes independent of its effect on viral DNA replication. Ectopic expression of BGLF4 in cells lacking the kinase gene stimulated the transcript levels of six late genes by 8- to 10-fold. Introduction of a BGLF4 mutant that eliminated its kinase activity did not stimulate late gene expression. In cells infected with wild-type EBV, siRNA to BGLF4 (siG4) markedly reduced late gene expression without compromising viral DNA replication. Synthesis of late products was restored upon expression of a form of BGLF4 resistant to the siRNA. Studying the EBV transcriptome using mRNA-seq during the late phase of the lytic cycle in the absence and presence of siG4 showed that BGLF4 controlled expression of 31 late genes. Analysis of the EBV transcriptome identified BGLF3 as a gene whose expression was reduced as a result of silencing BGLF4. Knockdown of BGLF3 markedly reduced late gene expression but had no effect on viral DNA replication or expression of BGLF4. Our findings reveal the presence of a late control locus encompassing BGLF3 and BGLF4 in the EBV genome, and provide evidence for the importance of both proteins in post-replication events that are necessary for expression of late genes.
format	article
author	Ayman El-Guindy Francesc Lopez-Giraldez Henri-Jacques Delecluse Jessica McKenzie George Miller
author_facet	Ayman El-Guindy Francesc Lopez-Giraldez Henri-Jacques Delecluse Jessica McKenzie George Miller
author_sort	Ayman El-Guindy
title	A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
title_short	A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
title_full	A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
title_fullStr	A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
title_full_unstemmed	A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
title_sort	locus encompassing the epstein-barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/962dfcb570484e159f9575acb51accf5
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A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.

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