HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hummel, M. Articles by Abecassis, M. Search for Related Content PubMed PubMed Citation Articles by Hummel, M. Articles by Abecassis, M. Agricola Articles by Hummel, M. Articles by Abecassis, M.

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

¹ Transplant Division, Department of Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
² Department of Microbiology and Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
³ Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA

Correspondence
Michael Abecassis
mabecass{at}nmh.org

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 suggest a role for DNA methylation in maintenance of viral latency, we find that the major immediate-early promoter/enhancer is not methylated in latently 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 suggest that these are not controlled by DNA methylation.

This article has been cited by other articles:

				J. Yuan, X. Liu, A. W. Wu, P. W. McGonagill, M. J. Keller, C. S. Galle, and J. L. Meier Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells J. Virol., July 1, 2009; 83(13): 6391 - 6403. [Abstract] [Full Text] [PDF]

				R. Humeniuk, P. J. Mishra, J. R. Bertino, and D. Banerjee Epigenetic reversal of acquired resistance to 5-fluorouracil treatment Mol. Cancer Ther., May 1, 2009; 8(5): 1045 - 1054. [Abstract] [Full Text] [PDF]

				X.-f. Liu, S. Yan, M. Abecassis, and M. Hummel Establishment of Murine Cytomegalovirus Latency In Vivo Is Associated with Changes in Histone Modifications and Recruitment of Transcriptional Repressors to the Major Immediate-Early Promoter J. Virol., November 1, 2008; 82(21): 10922 - 10931. [Abstract] [Full Text] [PDF]