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Journal of Virology, September 2002, p. 8797-8807, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8797-8807.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Viral Interferon Regulatory Factor 1 of Kaposi's Sarcoma-Associated Herpesvirus Interacts with a Cell Death Regulator, GRIM19, and Inhibits Interferon/Retinoic Acid-Induced Cell Death

Taegun Seo,1 Daeyoup Lee,1 Young Sam Shim,1 Jon E. Angell,2 Natesa V. Chidambaram,2 Dhananjaya V. Kalvakolanu,2 and Joonho Choe1*

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea,1 Department of Microbiology and Immunology, Greenebaum Cancer Center, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, Maryland 212012

Received 7 February 2002/ Accepted 4 June 2002

Kaposi's sarcoma-associated herpesvirus (KSHV) plays a significant role in the development of Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman's disease. The KSHV open reading frame K9 encodes the viral interferon (IFN) factor 1 (vIRF1), which downregulates IFN- and IRF-mediated transcriptional activation, and leads to cellular transformation in rodent fibroblasts and induction of tumors in nude mice. Using the yeast two-hybrid assay, we identified genes associated with retinoid-IFN-induced mortality-19 (GRIM19), which interacts directly with vIRF1, both in vivo and in vitro. The N-terminal region of vIRF1 is required for binding GRIM19. Colocalization of vIRF1 and GRIM19 was observed in 293T cells. The vIRF1 protein deregulates GRIM19-induced apoptosis in the presence of IFN/all-trans-retinoic acid (RA) and inhibits IFN/RA-induced cell death. Another DNA tumor viral protein, human papillomavirus type 16 E6, also binds GRIM19, suggesting that this is a general target of viral proteins. Our results collectively indicate that vIRF1 modulates IFN/RA-cell death signals via interactions with GRIM19.

* Corresponding author. Mailing address: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea. Phone: 82-42-869-2630. Fax: 82-42-869-5630. E-mail: jchoe{at}mail.kaist.ac.kr.

Journal of Virology, September 2002, p. 8797-8807, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8797-8807.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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