Murine cytomegalovirus paralyzes macrophages by blocking IFNγ-induced promoter assembly

Daniel L. Popkin, Mark A. Watson, Elizabeth Karaskov, Gavin P. Dunn, Rod Bremner, Herbert W. Virgin IV

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)14309-14314
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 25 2003

Keywords

  • Immune evasion
  • Microarray

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