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Journal of Virology, March 2001, p. 2692-2705, Vol. 75, No. 6
Institute for Virology, Johannes
Gutenberg-Universität, Mainz, Germany
Received 27 October 2000/Accepted 20 December 2000
The lungs are a major organ site of cytomegalovirus (CMV)
pathogenesis, latency, and recurrence. Previous work on murine CMV latency has documented a high load and an even distribution of viral
genomes in the lungs after the resolution of productive infection.
Initiation of the productive cycle requires expression of the
ie1/3 transcription unit, which is driven by the
immediate-early (IE) promoter P1/3 and generates IE1 and
IE3 transcripts by differential splicing. Latency is molecularly
defined by the absence of IE3 transcripts specifying the essential
transactivator protein IE3. In contrast, IE1 transcripts were found to
be generated focally and randomly, reflecting sporadic P1/3
activity. Selective generation of IE1 transcripts implies molecular control of latency operating after ie1/3 transcription
initiation. P1/3 is regulated by an upstream enhancer. It
is widely assumed that the viral transcriptional program is started by
activation of the enhancer through the binding of transcription
factors. Accordingly, stochastic transcription during latency might
reflect episodes of enhancer activation by the "noise" activity of
intrinsic transcription factors. In addition to ie1/3, the
enhancer controls gene ie2, which has its own promoter,
P2, and is transcribed in opposite direction. We show here
that ie2 is also randomly transcribed during latency.
Notably, however, ie1 and ie2 were found to be
expressed independently. We infer from this finding that expression of
the major IE genes is regulated asymmetrically and asynchronously via
the combined control unit P1/3 -E-P2. Our data
are consistent with a stochastic nature of enhancer action as it is
proposed by the "binary" or probability model.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.6.2692-2705.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Random, Asynchronous, and Asymmetric Transcriptional Activity of
Enhancer-Flanking Major Immediate-Early Genes ie1/3 and
ie2 during Murine Cytomegalovirus Latency in the
Lungs
*
Corresponding author. Mailing address: Institute for
Virology, Johannes Gutenberg-Universität, Hochhaus am
Augustusplatz, 55101 Mainz, Germany. Phone: 49-6131-393-3650. Fax:
49-6131-393-5604. E-mail:
Matthias.Reddehase{at}uni-mainz.de.
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