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Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter

Lytic infection of differentiated cell types with human cytomegalovirus (HCMV) results in the temporal expression of between 170–200 open reading frames (ORFs). A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and cellular mechan...

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Autores principales: Reeves, Matthew, Sinclair, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717713/
https://www.ncbi.nlm.nih.gov/pubmed/23736881
http://dx.doi.org/10.3390/v5061395
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author Reeves, Matthew
Sinclair, John
author_facet Reeves, Matthew
Sinclair, John
author_sort Reeves, Matthew
collection PubMed
description Lytic infection of differentiated cell types with human cytomegalovirus (HCMV) results in the temporal expression of between 170–200 open reading frames (ORFs). A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and cellular mechanisms associated with the co-ordinated recruitment of transcription complexes and, more recently, higher order chromatin structure. Importantly, HCMV, like all herpes viruses, establishes a lifelong latent infection of the host—one major site of latency being the undifferentiated haematopoietic progenitor cells resident in the bone marrow. Crucially, the establishment of latency is concomitant with the recruitment of cellular enzymes that promote extensive methylation of histones bound to the major immediate early promoter. As such, the repressive chromatin structure formed at the major immediate early promoter (MIEP) elicits inhibition of IE gene expression and is a major factor involved in maintenance of HCMV latency. However, it is becoming increasingly clear that a distinct subset of viral genes is also expressed during latency. In this review, we will discuss the mechanisms that control the expression of these latency-associated transcripts and illustrate that regulation of these latency-associated promoters is also subject to chromatin mediated regulation and that the instructive observations previously reported regarding the negative regulation of the MIEP during latency are paralleled in the regulation of latent gene expression.
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spelling pubmed-37177132013-07-22 Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter Reeves, Matthew Sinclair, John Viruses Review Lytic infection of differentiated cell types with human cytomegalovirus (HCMV) results in the temporal expression of between 170–200 open reading frames (ORFs). A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and cellular mechanisms associated with the co-ordinated recruitment of transcription complexes and, more recently, higher order chromatin structure. Importantly, HCMV, like all herpes viruses, establishes a lifelong latent infection of the host—one major site of latency being the undifferentiated haematopoietic progenitor cells resident in the bone marrow. Crucially, the establishment of latency is concomitant with the recruitment of cellular enzymes that promote extensive methylation of histones bound to the major immediate early promoter. As such, the repressive chromatin structure formed at the major immediate early promoter (MIEP) elicits inhibition of IE gene expression and is a major factor involved in maintenance of HCMV latency. However, it is becoming increasingly clear that a distinct subset of viral genes is also expressed during latency. In this review, we will discuss the mechanisms that control the expression of these latency-associated transcripts and illustrate that regulation of these latency-associated promoters is also subject to chromatin mediated regulation and that the instructive observations previously reported regarding the negative regulation of the MIEP during latency are paralleled in the regulation of latent gene expression. MDPI 2013-06-03 /pmc/articles/PMC3717713/ /pubmed/23736881 http://dx.doi.org/10.3390/v5061395 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Reeves, Matthew
Sinclair, John
Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
title Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
title_full Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
title_fullStr Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
title_full_unstemmed Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
title_short Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
title_sort regulation of human cytomegalovirus transcription in latency: beyond the major immediate-early promoter
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717713/
https://www.ncbi.nlm.nih.gov/pubmed/23736881
http://dx.doi.org/10.3390/v5061395
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