Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes.
The Kaposi's sarcoma herpesvirus (KSHV) has been identified as the etiologic agent of Kaposi's sarcoma (KS), but initial events leading to KS development remain unclear. Characterization of the KSHV genome reveals the presence of numerous potential oncogenes. To address their contribution to the initiation of the endothelial cell-derived KS tumor, we developed a novel transgenic mouse that enabled endothelial cell-specific infection in vivo using virus expressing candidate KSHV oncogenes. Here we show that transduction of one gene, vGPCR, was sufficient to induce angioproliferative tumors that strikingly resembled human KS. Endothelial cells expressing vGPCR were further able to promote tumor formation by cells expressing KSHV latent genes, suggestive of a cooperative role among viral genes in the promotion of Kaposi's sarcomagenesis.
Montaner
Silvia
S
Cell Growth Regulation Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Sodhi
Akrit
A
Molinolo
Alfredo
A
Bugge
Thomas H
TH
Sawai
Earl T
ET
He
Yunsheng
Y
Li
Yi
Y
Ray
Patricio E
PE
Gutkind
J Silvio
JS
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology / Q000648:ultrastructure / Q000821:virology; D005818:Genetic Engineering / Q000379:methods; D019288:Herpesvirus 8, Human / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D019707:Receptors, Chemokine / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000648:ultrastructure / Q000821:virology*; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000378:metabolism*
C105373:MEN1 protein, human; D009363:Neoplasm Proteins; C105181:ORF74 protein, Human herpesvirus 8; D011518:Proto-Oncogene Proteins; D019707:Receptors, Chemokine; D014764:Viral Proteins