title: The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor: Lessons on dysregulated angiogenesis from a viral oncogene.
abstract: Tumor viruses can induce cell transformation by overcoming cellular defense mechanisms and promoting the ungoverned proliferation of infected cells. To this end, functionally related viral oncogenes have evolved in disparate viruses to over-ride key proliferative and survival intracellular pathways, thus assuring efficient viral replication and contributing to tumor formation. Indeed, the study of viral oncogenes has been a powerful tool for disclosing fundamental insights into these basic cellular processes. In this regard, the Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8), the etiological agent of Kaposi's sarcoma (KS), is an exemplary model of an oncogenic virus that includes within its genome several homologues of cellular genes implicated in the regulation of cell proliferation and apoptosis. However, emerging evidence now points to a single KSHV gene, ORF74, encoding for the viral G protein-coupled receptor (vGPCR), as essential for KS development. Expressed in only a fraction of cells within KS lesions, this viral receptor induces tumorigenesis through both autocrine and paracrine mechanisms. Indeed, work from several laboratories has demonstrated that vGPCR can promote cell proliferation, enhance cell survival, modulate cell migration, stimulate angiogenesis, and recruit inflammatory cells, both in expressing cells, as well as in neighboring (bystander) cells. Examination of this powerful viral oncogene may expose novel targets for the treatment of patients with KS and could ultimately provide a unique perspective into how GPCRs, and specifically chemokine receptors, contribute to angiogenesis and tumorigenesis.
authors.affiliation: Department of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Jham
authors.forename: Silvia
authors.initials: S
authors.lastname: Montaner
mesh_terms: D005814:Genes, Viral / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D019899:Paracrine Communication; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000098:blood supply* / Q000235:genetics / Q000821:virology*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D043562:Receptors, G-Protein-Coupled; D020830:rac1 GTP-Binding Protein