Inhibition of interferon signaling by the Kaposi's sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein

Suzanne Fuld, Charles Cunningham, Kevin Klucher, Andrew J. Davison, David J. Blackbourn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

Interferon (IFN) signal transduction involves interferon regulatory factors (IRF). Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four IRF homologues: viral IRF 1 (vIRF-1) to vIRF-4. Previous functional studies revealed that the first exon of vIRF-2 inhibited alpha/beta interferon (IFN-α/β) signaling. We now show that full-length vIRF-2 protein, translated from two spliced exons, inhibited both IFN-α- and IFN-λ-driven transactivation of a reporter promoter containing the interferon stimulated response element (ISRE). Transactivation of the ISRE promoter by IRF-1 was negatively regulated by vIRF-2 protein as well. Transactivation of a full-length IFN-β reporter promoter by either IRF-3 or IRF-1, but not IRF-7, was also inhibited by vIRF-2 protein. Thus, vIRF-2 protein is an interferon induction antagonist that acts pleiotropically, presumably facilitating KSHV infection and dissemination in vivo.

Original languageEnglish
Pages (from-to)3092-3097
Number of pages6
JournalJournal of Virology
Volume80
Issue number6
DOIs
Publication statusPublished - Mar 2006

Bibliographical note

Acknowledgments
We thank Friedemann Weber for invaluable advice during the course of these studies, John Hiscott for the generous provision of many reagents, and Karl Burgess for technical help.
This study was supported in part by a Medical Research Council Ph.D. Studentship (S.F.) and grants from the Wellcome Trust (D.J.B., no. 059008/Z/99/Z; the Cunningham Trust (D.J.B., no. ACC/KM CT), the Association for International Cancer Research (D.J.B., no. 01-242), and Cancer Research UK (D.J.B., no. C7934).

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