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Journal of Virology, June 1999, p. 5043-5055, Vol. 73, No. 6
Institute for Virology, Johannes Gutenberg
University, Mainz, Germany
Received 4 January 1999/Accepted 11 March 1999
Transcription of the major immediate-early (MIE) genes of
cytomegaloviruses (CMV) is driven by a strong promoter-enhancer (MIEPE)
complex. Transactivator proteins encoded by these MIE genes are
essential for productive infection. Accordingly, the MIEPE is a crucial
control point, and its regulation by activators and repressors is
pertinent to virus replication. Since the MIEPE contains multiple
regulatory elements, it was reasonable to assume that specific sequence
motifs are irreplaceable for specifying the cell-type tropism and
replication pattern. Recent work on murine CMV infectivity (A. Angulo,
M. Messerle, U. H. Koszinowski, and P. Ghazal, J. Virol.
72:8502-8509, 1998) has documented the proposed enhancing function of
the enhancer in that its resection or its replacement by a
nonregulatory stuffer sequence resulted in a significant reduction of
infectivity, even though replication competence was maintained by a
basal activity of the spared authentic MIE promoter. Notably, full
capacity for productive in vitro infection of fibroblasts was restored
in recombinant viruses by the human CMV enhancer. Using two-color in
situ hybridization with MIEPE-specific polynucleotide probes, we
demonstrated that a murine CMV recombinant in which the complete murine
CMV MIEPE is replaced by the paralogous human CMV core promoter and
enhancer (recombinant virus mCMVhMIEPE) retained the potential to
replicate in vivo in all tissues relevant to CMV disease. Notably,
mCMVhMIEPE was also found to replicate in the liver, a site at which
transgenic hCMV MIEPE is silenced. We conclude that productive in vivo
infection with murine CMV does not strictly depend on a MIEPE
type-specific regulation.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
In Vivo Replication of Recombinant Murine
Cytomegalovirus Driven by the Paralogous Major Immediate-Early
Promoter-Enhancer of Human Cytomegalovirus
*
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.
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