Mapping of human herpesvirus 6 immediate-early 2 protein transactivation domains.
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.
Tomoiu
Andru
A
Laboratory of Virology, Rheumatology and Immunology Research Center, Centre de Recherche du CHUL and Faculty of Medicine, Laval University, 2705 Laurier Blvd., Room T1-49, Québec, Qc, Canada G1V 4G2. Andru.Tomoiu@crchul.ulaval.ca
Gravel
Annie
A
Flamand
Louis
L
D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D017930:Genes, Reporter; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008856:Microscopy, Fluorescence; D009154:Mutation; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D015533:Transcriptional Activation
D017874:Immediate-Early Proteins; D008156:Luciferases