Transgenic Expression of the Chemokine Receptor Encoded by Human Herpesvirus 8 Induces an Angioproliferative Disease Resembling Kaposi's Sarcoma

doi:10.1084/jem.191.3.445

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© The Rockefeller University Press, 0022-1007/2000/2/445/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 445-454

Original Article

Transgenic Expression of the Chemokine Receptor Encoded by Human Herpesvirus 8 Induces an Angioproliferative Disease Resembling Kaposi's Sarcoma

Tong-Yuan Yang^a, Shu-Cheng Chen^a, Michael W. Leach^b, Denise Manfra^a, Bernhard Homey^c, Maria Wiekowski^a, Lee Sullivan^a, Chung-Her Jenh^a, Satwant K. Narula^a, Stephen W. Chensue^d, and Sergio A. Lira^a
^a From the Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033
^b From the Department of Drug Safety and Metabolism, Schering-Plough Research Institute, Kenilworth, New Jersey 07033
^c Department of Immunology, DNAX Research Institute, Palo Alto, California 94304
^d Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109

Correspondence to: Sergio A. Lira, Dept. of Immunology, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033. Tel:908-740-3088 Fax:908-740-3084 E-mail:sergio.lira{at}spcorp.com.

Human herpesvirus 8 (HHV8, also known as Kaposi's sarcoma [KS]-associatedherpesvirus) has been implicated as an etiologic agent for KS,an angiogenic tumor composed of endothelial, inflammatory, andspindle cells. Here, we report that transgenic mice expressingthe HHV8-encoded chemokine receptor (viral G protein–coupledreceptor) within hematopoietic cells develop angioproliferativelesions in multiple organs that morphologically resemble KSlesions. These lesions are characterized by a spectrum of changesranging from erythematous maculae to vascular tumors, by thepresence of spindle and inflammatory cells, and by expressionof vGPCR, CD34, and vascular endothelial growth factor. We concludethat vGPCR contributes to the development of the angioproliferativelesions observed in these mice and suggest that this chemokinereceptor may play a role in the pathogenesis of KS in humans.

Key Words: ORF74, viral pathogenesis, animal model, angiogenesis, VEGF

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