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

被引:300
作者
Yang, TY
Chen, SC
Leach, MW
Manfra, D
Homey, B
Wiekowski, M
Sullivan, L
Jenh, CH
Narula, SK
Chensue, SW
Lira, SA
机构
[1] Schering Plough Corp, Res Inst, Dept Immunol, Kenilworth, NJ 07033 USA
[2] Schering Plough Corp, Res Inst, Dept Drug Safety & Metab, Kenilworth, NJ 07033 USA
[3] DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, Palo Alto, CA 94304 USA
[4] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
关键词
ORF74; viral pathogenesis; animal model; angiogenesis; VEGF;
D O I
10.1084/jem.191.3.445
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:445 / 453
页数:9
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