Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response

J Virol. 2004 Oct;78(20):10995-1006. doi: 10.1128/JVI.78.20.10995-11006.2004.


We have identified a cytomegalovirus virion protein capable of modulating the rapid induction of an interferon-like response in cells that follows virus binding and penetration. Functional genomics revealed a role for the major cytomegalovirus structural protein, pp65 (ppUL83), in counteracting this response. The underlying mechanism involves a differential impact of this structural protein on the regulation of interferon response factor 3 (IRF-3). In contrast, NF-kappaB is activated independent of pp65, and neither STAT1 nor STAT3 becomes activated by either virus. pp65 is sufficient to prevent the activation of IRF-3 when introduced alone into cells. pp65 acts by inhibiting nuclear accumulation of IRF-3 and is associated with a reduced IRF-3 phosphorylation state. Thus, this investigation shows that the major structural protein of cytomegalovirus is committed to the modulation of the IRF-3 response, a primary mediator of the type I interferon response. By subverting IRF-3, the virus escapes throwing a central alarm devoted to both immediate antiviral control and regulation of the immune response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Cytomegalovirus / genetics
  • Cytomegalovirus / pathogenicity*
  • DNA-Binding Proteins / metabolism*
  • Fibroblasts / virology
  • Gene Expression Regulation*
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon Type I / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphoproteins / genetics
  • Phosphoproteins / pharmacology*
  • Proteins / genetics
  • Proteins / metabolism
  • Proteome
  • Transcription Factors / metabolism*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / pharmacology*


  • DNA-Binding Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Type I
  • Phosphoproteins
  • Proteins
  • Proteome
  • Transcription Factors
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa