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Originally published as JGV in Press, 10.1099/vir.0.012245-0 on June 24, 2009 J Gen Virol 90 (2009), 2395-2401; DOI 10.1099/vir.0.012245-0

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Short Communication

Synergism between the components of the bipartite major immediate-early transcriptional enhancer of murine cytomegalovirus does not accelerate virus replication in cell culture and host tissues

Kai A. Kropp, Christian O. Simon{dagger}, Annette Fink, Angélique Renzaho, Birgit Kühnapfel, Jürgen Podlech, Matthias J. Reddehase and Natascha K. A. Grzimek

Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

Correspondence
Matthias J. Reddehase
Matthias.Reddehase{at}uni-mainz.de

Major immediate-early (MIE) transcriptional enhancers of cytomegaloviruses are key regulators that are regarded as determinants of virus replicative fitness and pathogenicity. The MIE locus of murine cytomegalovirus (mCMV) shows bidirectional gene-pair architecture, with a bipartite enhancer flanked by divergent core promoters. Here, we have constructed recombinant viruses mCMV-{Delta}Enh1 and mCMV-{Delta}Enh2 to study the impact of either enhancer component on bidirectional MIE gene transcription and on virus replication in cell culture and various host tissues that are relevant to CMV disease. The data revealed that the two unipartite enhancers can operate independently, but synergize in enhancing MIE gene expression early after infection. Kick-start transcription facilitated by the bipartite enhancer configuration, however, did not ultimately result in accelerated virus replication. We conclude that virus replication, once triggered, proceeds with a fixed speed and we propose that synergism between the components of the bipartite enhancer may rather increase the probability for transcription initiation.

{dagger}Present address: Roche Diagnostics, CH-6343 Rotkreuz, Switzerland.

A supplementary figure showing an alignment of sequencing data is available with the online version of this paper.






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