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

84 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

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