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Journal of Virology, July 2006, p. 7179-7185, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.01603-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Activation of NF-{kappa}B by the Latent vFLIP Gene of Kaposi's Sarcoma-Associated Herpesvirus Is Required for the Spindle Shape of Virus-Infected Endothelial Cells and Contributes to Their Proinflammatory Phenotype

Claudia Grossmann,1 Simona Podgrabinska,2 Mihaela Skobe,2 and Don Ganem1*

Howard Hughes Medical Institute and Departments of Microbiology and Medicine, University of California Medical Center, San Francisco, California 94143,1 Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 100292

Received 1 August 2005/ Accepted 20 April 2006

Kaposi's sarcoma (KS) is an inflammatory angioproliferative lesion induced by the infection of endothelial cells with the KS-associated herpesvirus (KSHV). Infected endothelial cells assume an elongated (spindle) shape that is one of the histologic signatures of KS. In vitro, latent viral infection of primary endothelial cells (but no other cell type) strikingly recapitulates these morphological findings. Here we report that the spindling phenotype involves major rearrangement of the actin cytoskeleton and can be attributed to the expression of a single viral protein, vFLIP, a known activator of NF-{kappa}B. Consistent with this, the inhibition of NF-{kappa}B activation blocks vFLIP-induced spindling in cultured endothelial cells. vFLIP expression in spindle cells also induces the production of a variety of proinflammatory cytokines and cell surface adhesion proteins that likely contribute to the inflammatory component of KS lesions.

* Corresponding author. Mailing address: University of California San Francisco, UCSF Box 0552, 513 Parnassuss Avenue, San Francisco, CA 94143. Phone: (415) 476-2826. Fax: (415) 476-0939. E-mail: ganem{at}cgl.ucsf.edu.

Journal of Virology, July 2006, p. 7179-7185, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.01603-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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