We have investigated beta interferon (IFN-beta) and IFN-alpha4 gene expression 
and activation of related transcription factors in mouse cytomegalovirus 
(MCMV)-infected fibroblasts. mRNA analysis demonstrated an initial phase of IFN 
gene induction upon MCMV infection, which was followed by a sustained 
MCMV-mediated simultaneous downregulation of IFN-beta and IFN-alpha4 gene 
expression. The induction of IFN transcription resulted from the activation of 
the components of the IFN-beta enhanceosome, i.e. IFN regulatory factor (IRF) 3, 
nuclear factor (NF)-kappaB, activating transcription factor (ATF)-2 and c-Jun. 
Activation of the transcription factors occurred rapidly and in a sequential 
order upon infection, but only lasted a while. As a consequence, IFN-alpha/beta 
gene expression became undetectable 6 h post-infection and throughout the MCMV 
replication cycle. This effect is based on an active interference since 
restimulation of IFN gene induction by further external stimuli (e.g. Sendai 
virus infection) was completely abolished. This inhibition required MCMV gene 
expression and was not observed in cells infected with UV-inactivated MCMV 
virions. The efficiency of inhibition is achieved by a concerted blockade of 
IkappaBalpha degradation and a lack of nuclear accumulation of IRF3 and 
ATF-2/c-Jun. Using an MCMV mutant lacking pM27, a signal transducer and 
activator of transcription (STAT) 2-specific inhibitor of Jak/STAT signalling, 
we found that the initial phase of IFN induction and the subsequent inhibition 
does not depend on the positive-IFN feedback loop. Our findings indicate that 
the MCMV-mediated downregulation of IFN transcription in fibroblasts relies on a 
large arsenal of inhibitory mechanisms targeting each pathway that contributes 
to the multiprotein enhanceosome complex.