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

Research output: Contribution to journalArticle

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

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Human Herpesvirus 8
Kaposi's Sarcoma
G-Protein-Coupled Receptors
Oncogenes
Primary Effusion Lymphoma
B-Cell Lymphoma
Open Reading Frames
Herpesviridae
Mitogens
Protein Kinases
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Carcinogenesis
B-Lymphocytes
Stem Cells
Cell Proliferation
Cytokines
Phenotype
Genes

ASJC Scopus subject areas

  • General

Cite this

G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. / Bais, Carlos; Santomasso, Bianca; Coso, Omar; Arvanitakis, Leandros; Raaka, Elizabeth Geras; Gutkind, J. Silvio; Asch, Adam S.; Cesarman, Ethel; Gerhengorn, Marvin C.; Mesri, Enrique A.

In: Nature, Vol. 391, No. 6662, 01.01.1998, p. 86-89.

Research output: Contribution to journalArticle

Bais, C, Santomasso, B, Coso, O, Arvanitakis, L, Raaka, EG, Gutkind, JS, Asch, AS, Cesarman, E, Gerhengorn, MC & Mesri, EA 1998, 'G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator', Nature, vol. 391, no. 6662, pp. 86-89. https://doi.org/10.1038/34193
Bais C, Santomasso B, Coso O, Arvanitakis L, Raaka EG, Gutkind JS et al. G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature. 1998 Jan 1;391(6662):86-89. https://doi.org/10.1038/34193
Bais, Carlos ; Santomasso, Bianca ; Coso, Omar ; Arvanitakis, Leandros ; Raaka, Elizabeth Geras ; Gutkind, J. Silvio ; Asch, Adam S. ; Cesarman, Ethel ; Gerhengorn, Marvin C. ; Mesri, Enrique A. / G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. In: Nature. 1998 ; Vol. 391, No. 6662. pp. 86-89.
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