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

C Bais, B Santomasso, O Coso, L Arvanitakis… - Nature, 1998 - nature.com
C Bais, B Santomasso, O Coso, L Arvanitakis, EG Raaka, JS Gutkind, AS Asch, E Cesarman
Nature, 1998nature.com
The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a γ-2 herpesvirus,,,, that is
implicated in the pathogenesis of Kaposi's sarcoma, and of primary effusion B-cell
lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and
PEL,,, it encodes putative oncogenes,, and genes that may cause Kaposi's sarcoma
pathogenesis by stimulating angiogenesis,,,. The G-protein-coupled receptor encoded by an
open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in …
Abstract
The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a γ-2 herpesvirus,,,, that is implicated in the pathogenesis of Kaposi's sarcoma, and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL,,, it encodes putative oncogenes,, and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis,,,. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in PEL, and stimulates signalling pathways linked to cell proliferation in a constitutive (agonist-independent) way. 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 phenotype mediated by vascular endothelial growth factor, an angiogenesis, and Kaposi's-spindle-cell growth factor,,. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines that are angiogenesis activators and mitogens for Kaposi's sarcoma cells 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.
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