Kaposi's Sarcoma-assoclated Herpesvirus-encoded vIRF-3 Stimulates the Transcriptional Activity of Cellullar IRF-3 and IRF-7

Barbora Lubyova, Merrill J. Kellum, Augusto J. Frisancho, Paula M. Pitha

Research output: Contribution to journalArticle

Abstract

Kaposi's sarcoma-associated herpesvirus has been linked to Kaposi's sarcoma, body cavity-based lymphoma, and Castleman's disease. The Kaposi's sarcoma-associated herpesvirus genome contains a cluster of open reading frames encoding proteins (vIRFs) with homology to the cellular transcription factors of the interferon regulatory factor family. vIRF-3, also called LANA2, is a latently expressed nuclear protein. Here we demonstrate that vIRF-3 directly interacts with cellular interferon regulatory factor (IRF) IRF-3, IRF-7, and the transcriptional co-activator CBP/p360. The mapping of the vIRF-3 binding domain revealed that vIRF-3 associates with both IRF-3 and IRF-7 through its C-terminal region. The p300 domain, which interacts with vIRF-3, is distinct from the previously identified IBM domain, to which both vIRF-1 and IRF-3 bind. Thus, in contrast to vIRF-1, vIRF-3 neither blocks the interaction between IRF-3 and p300 nor inhibits the histone acetylation. Although vIRF-3 is not a DNA-binding protein, it is recruited to the IFNA promoters via its interaction with IRF-3 and IRF-7. The presence of vIRF-3 in the enhanceosome assembled on the IFNA promoters increases binding of IRF-3, IRF-7, and acetylated histone H3 to this promoter region. Consequently, vIRF-3 stimulates the IRF-3- and IRF-7-mediated activation of type I interferon (IFNA and IFNB) genes and the synthesis of biologically active type I interferons in infected B cells. These studies illustrate that vIRF-3 and vIRF-1 have clearly distinct functions. In addition to its co-repressor activity, vIRF-3 can also act as a transcriptional activator on genes controlled by cellular IRF-3 and IRF-7.

Original languageEnglish (US)
Pages (from-to)7643-7654
Number of pages12
JournalJournal of Biological Chemistry
Volume279
Issue number9
DOIs
StatePublished - Feb 27 2004

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Interferon Regulatory Factor-7
Interferon Regulatory Factor-3
Kaposi's Sarcoma
Herpesviridae
Interferon Regulatory Factors
Human Herpesvirus 8
Interferon Type I
Genes
viral interferon regulatory factors
Histones
Giant Lymph Node Hyperplasia
Acetylation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kaposi's Sarcoma-assoclated Herpesvirus-encoded vIRF-3 Stimulates the Transcriptional Activity of Cellullar IRF-3 and IRF-7. / Lubyova, Barbora; Kellum, Merrill J.; Frisancho, Augusto J.; Pitha, Paula M.

In: Journal of Biological Chemistry, Vol. 279, No. 9, 27.02.2004, p. 7643-7654.

Research output: Contribution to journalArticle

Lubyova, Barbora ; Kellum, Merrill J. ; Frisancho, Augusto J. ; Pitha, Paula M. / Kaposi's Sarcoma-assoclated Herpesvirus-encoded vIRF-3 Stimulates the Transcriptional Activity of Cellullar IRF-3 and IRF-7. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 9. pp. 7643-7654.
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abstract = "Kaposi's sarcoma-associated herpesvirus has been linked to Kaposi's sarcoma, body cavity-based lymphoma, and Castleman's disease. The Kaposi's sarcoma-associated herpesvirus genome contains a cluster of open reading frames encoding proteins (vIRFs) with homology to the cellular transcription factors of the interferon regulatory factor family. vIRF-3, also called LANA2, is a latently expressed nuclear protein. Here we demonstrate that vIRF-3 directly interacts with cellular interferon regulatory factor (IRF) IRF-3, IRF-7, and the transcriptional co-activator CBP/p360. The mapping of the vIRF-3 binding domain revealed that vIRF-3 associates with both IRF-3 and IRF-7 through its C-terminal region. The p300 domain, which interacts with vIRF-3, is distinct from the previously identified IBM domain, to which both vIRF-1 and IRF-3 bind. Thus, in contrast to vIRF-1, vIRF-3 neither blocks the interaction between IRF-3 and p300 nor inhibits the histone acetylation. Although vIRF-3 is not a DNA-binding protein, it is recruited to the IFNA promoters via its interaction with IRF-3 and IRF-7. The presence of vIRF-3 in the enhanceosome assembled on the IFNA promoters increases binding of IRF-3, IRF-7, and acetylated histone H3 to this promoter region. Consequently, vIRF-3 stimulates the IRF-3- and IRF-7-mediated activation of type I interferon (IFNA and IFNB) genes and the synthesis of biologically active type I interferons in infected B cells. These studies illustrate that vIRF-3 and vIRF-1 have clearly distinct functions. In addition to its co-repressor activity, vIRF-3 can also act as a transcriptional activator on genes controlled by cellular IRF-3 and IRF-7.",
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