An in Vitro Model for the Regulation of Human Cytomegalovirus Latency and Reactivation in Dendritic Cells by Chromatin Remodelling

J Gen Virol. 2005 Nov;86(Pt 11):2949-2954. doi: 10.1099/vir.0.81161-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Chromatin Assembly and Disassembly / physiology*
  • Cytomegalovirus / physiology*
  • DNA, Viral / metabolism
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Gene Expression Regulation, Viral / genetics
  • Gene Expression Regulation, Viral / physiology*
  • Genes, Immediate-Early*
  • Humans
  • Virus Latency*

Substances

  • Antigens, CD34
  • DNA, Viral