This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grossmann, C. Articles by Ganem, D. Search for Related Content PubMed PubMed Citation Articles by Grossmann, C. Articles by Ganem, D.

Activation of NF-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

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-B. Consistent with this, the inhibition of NF-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.

This article has been cited by other articles:

• Ye, F.-C., Zhou, F.-C., Xie, J.-P., Kang, T., Greene, W., Kuhne, K., Lei, X.-F., Li, Q.-H., Gao, S.-J. (2008). Kaposi's Sarcoma-Associated Herpesvirus Latent Gene vFLIP Inhibits Viral Lytic Replication through NF-{kappa}B-Mediated Suppression of the AP-1 Pathway: a Novel Mechanism of Virus Control of Latency. J. Virol. 82: 4235-4249 [Abstract] [Full Text]  
• Efklidou, S., Bailey, R., Field, N., Noursadeghi, M., Collins, M. K. (2008). vFLIP from KSHV inhibits anoikis of primary endothelial cells. J. Cell Sci. 121: 450-457 [Abstract] [Full Text]  
• Matta, H., Mazzacurati, L., Schamus, S., Yang, T., Sun, Q., Chaudhary, P. M. (2007). Kaposi's Sarcoma-associated Herpesvirus (KSHV) Oncoprotein K13 Bypasses TRAFs and Directly Interacts with the I{kappa}B Kinase Complex to Selectively Activate NF-{kappa}B without JNK Activation. J. Biol. Chem. 282: 24858-24865 [Abstract] [Full Text]  
• Sadagopan, S., Sharma-Walia, N., Veettil, M. V., Raghu, H., Sivakumar, R., Bottero, V., Chandran, B. (2007). Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained NF-{kappa}B Activation during De Novo Infection of Primary Human Dermal Microvascular Endothelial Cells That Is Essential for Viral Gene Expression. J. Virol. 81: 3949-3968 [Abstract] [Full Text]  
• Xu, Y., Ganem, D. (2007). Induction of chemokine production by latent Kaposi's sarcoma-associated herpesvirus infection of endothelial cells. J. Gen. Virol. 88: 46-50 [Abstract] [Full Text]