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J Gen Virol 86 (2005), 2949-2954; DOI 10.1099/vir.0.81161-0

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© 2005 Society for General Microbiology

Short Communication

An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling

M. B. Reeves1, P. J. Lehner2, J. G. P. Sissons1 and J. H. Sinclair1

1 Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Level 5 Box 157, Hills Road, Cambridge CB2 2QQ, UK
2 Cambridge Institute for Medical Research, School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Level 5 Box 157, Hills Road, Cambridge CB2 2QQ, UK

Correspondence
J. H. Sinclair
js{at}mole.bio.cam.ac.uk

Human cytomegalovirus (HCMV) is a frequent cause of major disease following primary infection or reactivation from latency in immunocompromised patients. Infection of non-permissive mononuclear cells is used for analyses of HCMV latency in vitro. Using this approach, it is shown here that repression of lytic gene expression following experimental infection of CD34+ cells, a site of HCMV latency in vivo, correlates with recruitment of repressive chromatin around the major immediate-early promoter (MIEP). Furthermore, long-term culture of CD34+ cells results in carriage of viral genomes in which the MIEP remains associated with transcriptionally repressive chromatin. Finally, specific differentiation of long-term cultures of infected CD34+ cells to mature dendritic cells results in acetylation of histones bound to the MIEP, concomitant loss of heterochromatin protein 1 and the reactivation of HCMV. These data are consistent with ex vivo analyses of latency and may provide a model for further analyses of the mechanisms involved during latency and reactivation.

Published online ahead of print on 31 August 2005 as DOI 10.1099/vir.0.81161-0.




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