Transcriptional reactivation of murine cytomegalovirus ie gene expression by 5-aza-2′-deoxycytidine and trichostatin A in latently infected cells despite lack of methylation of the major immediate-early promoter

Mary Hummel, Shixian Yan, Zhigao Li, Thomas K. Varghese, Michael Abecassis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

We have used a spleen explant model to investigate mechanisms of murine cytomegalovirus latency and reactivation. Induction of immediate-early (ie) gene expression occurs in explants after approximately 9 days in culture and virus reactivation follows induction of ie gene expression with kinetics similar to that of productive infection in vitro. This occurs independently of TNF receptor signalling. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor trichostatin A results in more rapid induction of ie gene expression and reactivation of virus. Despite these results, which suggests a role for DNA methylation in maintenance of viral latency, we find that the major immediate-early promoter/enchancer is not methylated in latenly infected mice. Our results support the hypothesis that latency is maintained by epigenetic control of ie gene expression, and that induction of ie gene expression leads to reactivation of virus, but suggests that these are not controlled by DNA methylation.

Original languageEnglish (US)
Pages (from-to)1097-1102
Number of pages6
JournalJournal of General Virology
Volume88
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Transcriptional reactivation of murine cytomegalovirus ie gene expression by 5-aza-2′-deoxycytidine and trichostatin A in latently infected cells despite lack of methylation of the major immediate-early promoter'. Together they form a unique fingerprint.

Cite this