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Journal of Virology, March 2006, p. 3092-3097, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.3092-3097.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of Interferon Signaling by the Kaposi's Sarcoma-Associated Herpesvirus Full-Length Viral Interferon Regulatory Factor 2 Protein

Suzanne Fuld,1 Charles Cunningham,2 Kevin Klucher,3 Andrew J. Davison,2 and David J. Blackbourn4*

Lab21 Limited, Unit 184, The Science Park, Cambridge, CB4 0GA, United Kingdom,1 MRC Virology Unit, Church Street, Glasgow G11 5JR, United Kingdom,2 Department of Cytokine Biology, ZymoGenetics, Inc., 1201 Eastlake Ave. E., Seattle, Washington 98102,3 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, United Kingdom4

Received 18 April 2005/ Accepted 28 December 2005

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-{alpha}/ß) signaling. We now show that full-length vIRF-2 protein, translated from two spliced exons, inhibited both IFN-{alpha}- and IFN-{lambda}-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-ß 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.

* Corresponding author. Mailing address: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Dr., Birmingham B15 2TT, United Kingdom. Phone: 44 (0)121 415-8804. Fax: 44 (0)121 414-4486. E-mail: d.j.blackbourn{at}bham.ac.uk.

Journal of Virology, March 2006, p. 3092-3097, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.3092-3097.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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