A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.

Epstein-Barr virus (EBV), an oncogenic human herpesvirus, induces cell proliferation after infection of resting B lymphocytes, its reservoir in vivo. The viral latent proteins are necessary for permanent B cell growth, but it is unknown whether they are sufficient. EBV was recently found to encode m...

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Autores principales:	Regina Feederle, Sarah D Linnstaedt, Helmut Bannert, Helge Lips, Maja Bencun, Bryan R Cullen, Henri-Jacques Delecluse
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/59e276d0317c489facca6687335d414f
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spelling	oai:doaj.org-article:59e276d0317c489facca6687335d414f2021-11-18T06:03:36ZA viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.1553-73661553-737410.1371/journal.ppat.1001294https://doaj.org/article/59e276d0317c489facca6687335d414f2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21379335/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Epstein-Barr virus (EBV), an oncogenic human herpesvirus, induces cell proliferation after infection of resting B lymphocytes, its reservoir in vivo. The viral latent proteins are necessary for permanent B cell growth, but it is unknown whether they are sufficient. EBV was recently found to encode microRNAs (miRNAs) that are expressed in infected B cells and in some EBV-associated lymphomas. EBV miRNAs are grouped into two clusters located either adjacent to the BHRF1 gene or in introns contained within the viral BART transcripts. To understand the role of the BHRF1 miRNA cluster, we have constructed a virus mutant that lacks all its three members (Δ123) and a revertant virus. Here we show that the B cell transforming capacity of the Δ123 EBV mutant is reduced by more than 20-fold, relative to wild type or revertant viruses. B cells exposed to the knock-out virus displayed slower growth, and exhibited a two-fold reduction in the percentage of cells entering the cell cycle S phase. Furthermore, they displayed higher latent gene expression levels and latent protein production than their wild type counterparts. Therefore, the BHRF1 miRNAs accelerate B cell expansion at lower latent gene expression levels. Thus, this miRNA cluster simultaneously enhances expansion of the virus reservoir and reduces the viral antigenic load, two features that have the potential to facilitate persistence of the virus in the infected host. Thus, the EBV BHRF1 miRNAs may represent new therapeutic targets for the treatment of some EBV-associated lymphomas.Regina FeederleSarah D LinnstaedtHelmut BannertHelge LipsMaja BencunBryan R CullenHenri-Jacques DeleclusePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 2, p e1001294 (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 Regina Feederle Sarah D Linnstaedt Helmut Bannert Helge Lips Maja Bencun Bryan R Cullen Henri-Jacques Delecluse A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.
description	Epstein-Barr virus (EBV), an oncogenic human herpesvirus, induces cell proliferation after infection of resting B lymphocytes, its reservoir in vivo. The viral latent proteins are necessary for permanent B cell growth, but it is unknown whether they are sufficient. EBV was recently found to encode microRNAs (miRNAs) that are expressed in infected B cells and in some EBV-associated lymphomas. EBV miRNAs are grouped into two clusters located either adjacent to the BHRF1 gene or in introns contained within the viral BART transcripts. To understand the role of the BHRF1 miRNA cluster, we have constructed a virus mutant that lacks all its three members (Δ123) and a revertant virus. Here we show that the B cell transforming capacity of the Δ123 EBV mutant is reduced by more than 20-fold, relative to wild type or revertant viruses. B cells exposed to the knock-out virus displayed slower growth, and exhibited a two-fold reduction in the percentage of cells entering the cell cycle S phase. Furthermore, they displayed higher latent gene expression levels and latent protein production than their wild type counterparts. Therefore, the BHRF1 miRNAs accelerate B cell expansion at lower latent gene expression levels. Thus, this miRNA cluster simultaneously enhances expansion of the virus reservoir and reduces the viral antigenic load, two features that have the potential to facilitate persistence of the virus in the infected host. Thus, the EBV BHRF1 miRNAs may represent new therapeutic targets for the treatment of some EBV-associated lymphomas.
format	article
author	Regina Feederle Sarah D Linnstaedt Helmut Bannert Helge Lips Maja Bencun Bryan R Cullen Henri-Jacques Delecluse
author_facet	Regina Feederle Sarah D Linnstaedt Helmut Bannert Helge Lips Maja Bencun Bryan R Cullen Henri-Jacques Delecluse
author_sort	Regina Feederle
title	A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.
title_short	A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.
title_full	A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.
title_fullStr	A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.
title_full_unstemmed	A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.
title_sort	viral microrna cluster strongly potentiates the transforming properties of a human herpesvirus.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/59e276d0317c489facca6687335d414f
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A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus.

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