JVI Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kurz, S. K.
Right arrow Articles by Reddehase, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kurz, S. K.
Right arrow Articles by Reddehase, M. J.

 Previous Article  |  Next Article 

Journal of Virology, October 1999, p. 8612-8622, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Patchwork Pattern of Transcriptional Reactivation in the Lungs Indicates Sequential Checkpoints in the Transition from Murine Cytomegalovirus Latency to Recurrence

Sabine K. Kurzdagger and Matthias J. Reddehase*

Institute for Virology, Johannes Gutenberg-University, Mainz, Germany

Received 28 April 1999/Accepted 14 June 1999

The lungs are a significant organ site of murine cytomegalovirus (mCMV) latency. We have shown that activity of the major immediate-early promoter (MIEP), which drives the transcription from the ie1-ie3 transcription unit, does not inevitably initiate the productive cycle (S. K. Kurz, M. Rapp, H.-P. Steffens, N. K. A. Grzimek, S. Schmalz, and M. J. Reddehase, J. Virol. 73:482-494, 1999). Thus, even though MIEP activity governed by the MIEP-enhancer is unquestionably the first condition for recurrence, regulation of the enhancer by transcription factors is not the only mechanism controlling latency. Specifically, during latency, focal and stochastic MIEP activity in lung tissue was found to selectively generate IE1 transcripts, while transactivator-specifying IE3 transcripts were missing. This suggested a control of mCMV latency that is effectual at IE1-IE3 precursor mRNA cotranscriptional processing. Here we have used this model for studying the kinetics of reactivation and recurrence in individual lung tissue pieces after hematoablative, genotoxic treatment. Notably, reactivation was triggered, but the number of transcriptionally active foci in the lungs did not increase over time. This result is not compatible with a model of spontaneous reactivations accumulating after withdrawal of immune control. Instead, the data support the idea that reactivation is an induced event. In some pieces, focal reactivation generated IE3 transcripts but not gB transcripts, while other pieces contained foci that had proceeded to gB transcription, and only a few foci actually reached the state of virus recurrence. This finding indicates the existence of several sequentially ordered control points in the transition from mCMV latency to recurrence.


* Corresponding author. Mailing address: Institute for Virology, Johannes Gutenberg-University, Hochhaus am Augustusplatz, 55101 Mainz, Germany. Phone: 49-6131-173650. Fax: 49-6131-395604. E-mail: Matthias.Reddehase{at}uni-mainz.de.

dagger Present address: Howard Hughes Medical Institute (c/o M. R. Green), University of Massachusetts Medical Center, Worcester, MA 01605.


Journal of Virology, October 1999, p. 8612-8622, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Mol. Cell. Biol. Microbiol. Mol. Biol. Rev.
Clin. Vaccine Immunol. ALL ASM JOURNALS

Copyright © 1999 by the American Society for Microbiology. All rights reserved.