title: 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.
abstract: 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-DeltaEnh1 and mCMV-DeltaEnh2 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.
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Kai A
authors: KA
authors: Kropp
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Christian O
authors: CO
authors: Simon
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Annette
authors: A
authors: Fink
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Angélique
authors: A
authors: Renzaho
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Birgit
authors: B
authors: Kühnapfel
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Jürgen
authors: J
authors: Podlech
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Matthias J
authors: MJ
authors: Reddehase
authors: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors: Natascha K A
authors: NKA
authors: Grzimek
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004261:DNA Replication / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics / Q000502:physiology; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D016867:Immunocompromised Host; D051379:Mice; D014158:Transcription, Genetic; D014779:Virus Replication / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D017874:Immediate-Early Proteins; C044582:immediate-early proteins, cytomegalovirus