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J Virol, July 1998, p. 5433-5440, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor

Mengtao Li,1 Heuiran Lee,1 Jie Guo,1 Frank Neipel,2 Bernhard Fleckenstein,2 Keiko Ozato,3 and Jae U. Jung1,*

New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 017721; Institute fur Klinishe und Molekulare Virologies, Friedrich-Alexander Universitat, D-8520 Erlangen, Germany2; and Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 208923

Received 29 October 1997/Accepted 23 March 1998

Interferons (IFNs) are a family of multifunctional cytokines with antiviral activities. The K9 open reading frame of Kaposi's sarcoma-associated herpesvirus (KSHV) exhibits significant homology with cellular IFN regulatory factors (IRFs). We have investigated the functional consequence of K9 expression in IFN-mediated signal transduction. Expression of K9 dramatically repressed transcriptional activation induced by IFN-alpha , -beta , and -gamma . Further, it induced transformation of NIH 3T3 cells, resulting in morphologic changes, focus formation, and growth in reduced-serum conditions. The expression of antisense K9 in KSHV-infected BCBL-1 cells consistently increased IFN-mediated transcriptional activation but drastically decreased the expression of certain KSHV genes. Thus, the K9 gene of KSHV encodes the first virus-encoded IRF (v-IRF) which functions as a repressor for cellular IFN-mediated signal transduction. In addition, v-IRF likely plays an important role in regulating KSHV gene expression. These results suggest that KSHV employs an unique mechanism to antagonize IFN-mediated antiviral activity by harboring a functional v-IRF.

* Corresponding author. Mailing address: New England Regional Primate Research Center, 1 Pine Hill Dr., Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 624-8190. E-mail: jjung{at}warren.med.harvard.edu.

J Virol, July 1998, p. 5433-5440, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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