Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma.
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.
Yang
T Y
TY
Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Chen
S C
SC
Leach
M W
MW
Manfra
D
D
Homey
B
B
Wiekowski
M
M
Sullivan
L
L
Jenh
C H
CH
Narula
S K
SK
Chensue
S W
SW
Lira
S A
SA
D000818:Animals; D018801:CD2 Antigens / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006338:Heart Neoplasms / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000235:genetics*; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000648:ultrastructure / Q000821:virology*; D012878:Skin Neoplasms / Q000473:pathology; D014412:Tumor Virus Infections; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*
D018801:CD2 Antigens; D016228:Endothelial Growth Factors; C115448:G protein-coupled receptor, Human herpesvirus 8; D008222:Lymphokines; D019707:Receptors, Chemokine; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014764:Viral Proteins; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor