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, Enrique A. Mesri

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715 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)86-89
Number of pages4
JournalNature
Volume391
Issue number6662
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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    Bais, C., Santomasso, B., Coso, O., Arvanitakis, L., Raaka, E. G., Gutkind, J. S., Asch, A. S., Cesarman, E., Gerhengorn, M. C., & Mesri, E. A. (1998). G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature, 391(6662), 86-89. https://doi.org/10.1038/34193