title: Murine cytomegalovirus paralyzes macrophages by blocking IFN gamma-induced promoter assembly.
abstract: Macrophages (M phi) are activated by IFN gamma and are important cellular targets for infection by human and murine cytomegalovirus (MCMV), making it advantageous for CMVs to block IFN gamma-induced M phi differentiation. We found that MCMV infection inhibited IFN gamma regulation of many genes in M phi. MCMV infection blocked IFN gamma 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 IFN gamma-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 IFN gamma-responsive chromosomal class II transactivator promoter revealed that MCMV infection blocked IFN gamma-induced promoter assembly, allowing the virus to transcriptionally paralyze infected M phi responses while allowing basal transcription to proceed.
authors: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Daniel L
authors: DL
authors: Popkin
authors: Mark A
authors: MA
authors: Watson
authors: Elizabeth
authors: E
authors: Karaskov
authors: Gavin P
authors: GP
authors: Dunn
authors: Rod
authors: R
authors: Bremner
authors: Herbert W
authors: HW
authors: Virgin
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000821:virology; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000472:pathogenicity*; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; C083728:MHC class II transactivator protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma