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J Gen Virol. 2005 Nov;86(Pt 11):2949-54.

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

Author information

1
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Level 5 Box 157, Hills Road, Cambridge CB2 2QQ, UK.

Abstract

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.

PMID:
16227215
DOI:
10.1099/vir.0.81161-0
[Indexed for MEDLINE]

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