G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator

Carlos Bais, Bianca Santomasso, Omar Coso, Leandros Arvanitakis, Elizabeth Geras Raaka, J. Silvio Gutkind, Adam S. Asch, Ethel Cesarman, Marvin C. Gerhengorn and Enrique A. Mesri ()
Additional contact information
Carlos Bais: Laboratory of Viral Oncogenesis, Cornell University Medical College
Bianca Santomasso: Laboratory of Viral Oncogenesis, Cornell University Medical College
Omar Coso: Molecular Signaling Unit, Laboratory of Cellular Development and Oncology, NIDR, NIH
Leandros Arvanitakis: Cornell University Medical College
Elizabeth Geras Raaka: Cornell University Medical College
J. Silvio Gutkind: Molecular Signaling Unit, Laboratory of Cellular Development and Oncology, NIDR, NIH
Adam S. Asch: Cornell University Medical College
Ethel Cesarman: Cornell University Medical College
Marvin C. Gerhengorn: Cornell University Medical College
Enrique A. Mesri: Laboratory of Viral Oncogenesis, Cornell University Medical College

Nature, 1998, vol. 391, issue 6662, 86-89

Abstract: Abstract The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a γ-2 herpesvirus1,2,3,4,5 that is implicated in the pathogenesis of Kaposi's sarcoma1,5 and of primary effusion B-cell lymphomas (PELs)6. KSHV infects malignant and progenitor cells of Kaposi's sarcoma7 and PEL2,6,8, it encodes putative oncogenes4,5,9 and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis4,5,9,10. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV9 is expressed in Kaposi's sarcoma lesions and in PEL9,11 and stimulates signalling pathways linked to cell proliferation12 in a constitutive (agonist-independent) way12. Here we show that signalling by this KSHV G-protein-coupled receptor leads to cell transformation and tumorigenicity, and induces a switch to an angiogenic phenotype13 mediated by vascular endothelial growth factor14, an angiogenesis13,14 and Kaposi's-spindle-cell growth factor15,16,17. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines18 that are angiogenesis activators19 and mitogens for Kaposi's sarcoma cells10 and B cells. We conclude that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in KSHV-mediated oncogenesis.

Date: 1998
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DOI: 10.1038/34193

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