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 P(1/3) 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 P(1/3) activity. 
Selective generation of IE1 transcripts implies molecular control of latency 
operating after ie1/3 transcription initiation. P(1/3) 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, P(2), 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 P(1/3) -E-P(2). Our data are 
consistent with a stochastic nature of enhancer action as it is proposed by the 
"binary" or probability model.