Murine cytomegalovirus paralyzes macrophages by blocking IFNγ-induced promoter assembly

Macrophages (Mphi) are activated by IFNgamma and are important cellular targets for infection by human and murine cytomegalovirus (MCMV), making it advantageous for CMVs to block IFNgamma-induced Mphi differentiation. We found that MCMV infection inhibited IFNgamma regulation of many genes in Mphi. MCMV infection blocked IFNgamma 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 11 transactivator-dependent and independent promoters. MCMV did not alter basal transcription from IFNgamma-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 IFNgamma-responsive chromosomal class 11 transactivator promoter revealed that MCMV infection blocked IFNgamma-induced promoter assembly, allowing the virus to transcriptionally paralyze infected Mphi responses while allowing basal transcription to proceed.