title: A G protein-coupled receptor encoded by rhesus rhadinovirus is similar to ORF74 of Kaposi's sarcoma-associated herpesvirus.
abstract: Rhesus rhadinovirus (RRV) is a gamma-2 herpesvirus and is the rhesus macaque homologue of human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus. DNA sequence analysis of RRV indicates that it shares numerous open reading frames (ORFs) with HHV-8, including one (ORF74) encoding a seven-transmembrane-spanning G protein-coupled receptor (GPCR) with similarity to cellular chemokine receptors. Examination of the predicted amino acid sequence of RRV ORF74 reveals that it encodes a seven-transmembrane-spanning GPCR sharing 40.8% amino acid sequence identity with HHV-8 ORF74 and 24.1% amino acid sequence identity with rhesus macaque CXCR2. In addition, immunofluorescence studies indicate that an epitope-tagged version of RRV ORF74 is expressed on the surfaces of transfected cells, suggesting that this protein is in fact a membrane receptor. In in vitro cell culture assays, RRV ORF74 possesses transforming potential, as NIH 3T3 clones stably expressing the receptor demonstrate an increased ability to grow in soft agarose and to induce tumor formation in nude mice. Further analysis of RRV ORF74 indicates that expression of the receptor in NIH 3T3 cells causes an increased secretion of vascular endothelial growth factor and activation of the ERK1/2 (p44/42) mitogen-activated protein kinase signaling pathway. The results of these studies suggest that RRV ORF74 encodes a GPCR with properties similar to those of its homologue in HHV-8 and that this gene may play a role in RRV-associated pathogenesis.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University West Campus, Beaverton, Oregon 97006, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Estep
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Scott W
authors.initials: SW
authors.lastname: Wong
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D008253:Macaca mulatta / Q000821:virology*; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011956:Receptors, Cell Surface / Q000737:chemistry*; D019707:Receptors, Chemokine / Q000737:chemistry*; D023063:Receptors, Interleukin-8B / Q000737:chemistry; D018144:Rhadinovirus / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C105181:ORF74 protein, Human herpesvirus 8; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014764:Viral Proteins; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins