Murine cytomegalovirus paralyzes macrophages by blocking IFNγ-induced promoter assembly

Macrophages (Mψ) are activated by IFNγ and are important cellular targets for infection by human and murine cytomegalovirus (MCMV), making it advantageous for CMVs to block IFNγ-induced Mψ differentiation. We found that MCMV infection inhibited IFNγ regulation of many genes in Mψ. MCMV infection blocked IFNγ responses at the level of transcription without blocking Janus kinase/signal transducer and activator of transcription pathway activation and targeted IFN response factor 1- and class II transactivator-dependent and independent promoters. MCMV did not alter basal transcription from IFNγ-responsive promoters and left the majority of cellular transcripts unchanged even after 48 h of infection. The effects of MCMV infection were specific to chromosomal rather than transiently transfected promoters. Characterization of the IFNγ-responsive chromosomal class II transactivator promoter revealed that MCMV infection blocked IFNγ-induced promoter assembly, allowing the virus to transcriptionally paralyze infected Mψ responses while allowing basal transcription to proceed.