Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma

Tong Yuan Yang, Shu Cheng Chen, Michael W. Leach, Denise Manfra, Bernhard Homey, Maria Wiekowski, Lee Sullivan, Chung Her Jenh, Satwant K. Narula, Stephen W. Chensue, Sergio A. Lira

Research output: Contribution to journalArticlepeer-review

369 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)445-453
Number of pages9
JournalJournal of Experimental Medicine
Volume191
Issue number3
DOIs
StatePublished - 7 Feb 2000
Externally publishedYes

Keywords

  • Angiogenesis
  • Animal model
  • ORF74
  • VEGF
  • Viral pathogenesis

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