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Regulation of human cytomegalovirus transcription in latency: beyond the major immediate-early promoter

Reeves, M; Sinclair, J; (2013) Regulation of human cytomegalovirus transcription in latency: beyond the major immediate-early promoter. Viruses , 5 (6) 1395 - 1413. 10.3390/v5061395. Green open access

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Abstract

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.

Type: Article
Title: Regulation of human cytomegalovirus transcription in latency: beyond the major immediate-early promoter
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/v5061395
Publisher version: http://dx.doi.org/10.3390/v5061395
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ PMCID: PMC3717713
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1406855
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