The Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 inhibits cellular IRF-5
Wies E, Hahn A, Schmidt K, Viebahn C, Rohland N, Lux A, Schellhorn T, Holzer A, Jung JU, Neipel F (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 284
Pages Range: 8525-8538
Journal Issue: 13
Abstract
Kaposi's sarcoma-associated herpesvirus encodes four genes with homology to the family of interferon regulatory factors (IRFs). At least one of these viral IRFs, vIRF-3, is expressed in latently Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphoma (PEL) cells and is essential for the survival of PEL cells. We now report that vIRF-3 interacts with cellular IRF-5, thereby inhibiting binding of IRF-5 to interferon-responsive promoter elements. Consequently, vIRF-3 blocked IRF-5-mediated promoter activation. A central double helix motif present in vIRF-3 was sufficient to abrogate both DNA binding and transcriptional transactivation by IRF-5. Upon DNA damage or activation of the interferon or Toll-like receptor pathways, cytoplasmic IRF-5 has been reported to be translocated to the nucleus, which results in induction of both p53-independent apoptosis and p21-mediated cell cycle arrest. We report here that IRF-5 is present in the nuclei of PEL cells without interferon stimulation. Silencing of vIRF-3 expression in PEL cells was accompanied by increased sensitivity to interferon- mediated apoptosis and up-regulation of IRF-5 target genes. In addition, vIRF-3 antagonized IRF-5-mediated activation of the p21 promoter. The data presented here indicate that vIRF-3 contributes to immune evasion and sustained proliferation of PEL cells by releasing IRF-5 from transcription complexes. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors with CRIS profile
Alexander Hahn
Institute of Clinical and Molecular Virology
Anja Lux
Professur für Integrated Immunology
Frank Neipel
Institute of Clinical and Molecular Virology
Involved external institutions
United States (USA) (US)How to cite
APA:
Wies, E., Hahn, A., Schmidt, K., Viebahn, C., Rohland, N., Lux, A.,... Neipel, F. (2009). The Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 inhibits cellular IRF-5. Journal of Biological Chemistry, 284(13), 8525-8538. https://doi.org/10.1074/jbc.M809252200
MLA:
Wies, Effi, et al. "The Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 inhibits cellular IRF-5." Journal of Biological Chemistry 284.13 (2009): 8525-8538.
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