Mapping of human herpesvirus 6 immediate-early 2 protein transactivation domains

Virology. 2006 Oct 10;354(1):91-102. doi: 10.1016/j.virol.2006.06.030. Epub 2006 Aug 1.


The immediate-early 2 (IE2) protein of human herpesvirus 6 (HHV-6) is a potent transactivator of multiple cellular and viral promoters. Deletion mutants of HHV-6 variant A IE2 allowed us to map functional transactivation domains acting on complex and minimal promoter sequences. This mapping showed that both the N-terminal and C-terminal domains of IE2 are required for efficient transactivation, and that deletion of the C-terminal (1397-1466) tail of IE2 drastically reduces both transactivation and the intranuclear distribution of IE2. Moreover, we determined that the ATF/CRE binding site within the HHV-6A polymerase promoter is not required for efficient transactivation by IE2, whereas the R3 repeat region of the putative immediate-early promoter of HHV-6A is responsive to and positively regulated by IE2. These results contrast sharply to that of human cytomegalovirus (HCMV) IE2, which down-regulates its promoter. Our characterization of HHV-6 IE2 transactivating activity provides a better understanding of the complex interactions of this protein with the viral and cellular transcription machinery and highlights significant differences with the IE2 protein of HCMV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Nucleus / chemistry
  • Genes, Reporter
  • Herpesvirus 6, Human / genetics*
  • Herpesvirus 6, Human / physiology
  • Humans
  • Immediate-Early Proteins / analysis
  • Immediate-Early Proteins / chemistry*
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / physiology*
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Microscopy, Fluorescence
  • Mutation
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Sequence Deletion
  • Transcriptional Activation*


  • Immediate-Early Proteins
  • Luciferases