Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation.
Kaposi's sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus 8, or HHV 8) is a virus that is consistently present in Kaposi's sarcoma and in primary-effusion (body-cavity-based) lymphomas, malignancies that occur frequently, but not exclusively, in AIDS patients. KSHV is a gamma herpesvirus with homology to herpesvirus Saimiri and Epstein-Barr virus, both of which can transform lymphocytes. Cloning of a KSHV genome fragment revealed the presence of an open reading frame encoding a putative G-protein-coupled receptor that is homologous to a G-protein-coupled receptor encoded by herpesvirus Saimiri and to human interleukin-8 receptors. Here we show that the KSHV G-protein-coupled receptor is a bona fide signalling receptor which has constitutive (agonist-independent) activity in the phosphoinositide-inositoltrisphosphate-protein kinase C pathway. Furthermore, the KSHV G-protein-coupled receptor stimulates cellular proliferation, making it a candidate viral oncogene.
Arvanitakis
L
L
Department of Pathology, Cornell University Medical College, New York 10021, USA.
Geras-Raaka
E
E
Varma
A
A
Gershengorn
M C
MC
Cesarman
E
E
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001667:Binding, Competitive; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D002472:Cell Transformation, Viral; D018925:Chemokines / Q000378:metabolism; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D051381:Rats; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000821:virology; D015290:Second Messenger Systems; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; D018925:Chemokines; D007295:Inositol Phosphates; D016209:Interleukin-8; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014764:Viral Proteins; D008156:Luciferases; D019204:GTP-Binding Proteins