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Science 307 (5710): 739-741

Copyright © 2005 by the American Association for the Advancement of Science

The Kaposin B Protein of KSHV Activates the p38/MK2 Pathway and Stabilizes Cytokine mRNAs

Craig McCormick, and Don Ganem*

Abstract: Cytokine production plays a critical role in diseases caused by Kaposi's sarcoma–associated herpesvirus (KSHV). Here we show that a latent KSHV gene product, kaposin B, increases the expression of cytokines by blocking the degradation of their messenger RNAs (mRNAs). Cytokine transcripts are normally unstable because they contain AU-rich elements (AREs) in their 3' noncoding regions that target them for degradation. Kaposin B reverses this instability by binding to and activating the kinase MK2, a target of the p38 mitogen-activated protein kinase signaling pathway and a known inhibitor of ARE-mRNA decay. These findings define an important mechanism linking latent KSHV infection to cytokine production, and also illustrate a distinctive mode by which viruses can selectively modulate mRNA turnover.

Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Medicine, University of California, San Francisco, CA 94143, USA.

* To whom correspondence should be addressed. E-mail: ganem{at}cgl.ucsf.edu

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