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Virology. 2006 Oct 10;354(1):91-102. Epub 2006 Aug 1.

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

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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, Qu├ębec, Qc, Canada G1V 4G2.


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.

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