Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation.
Arvanitakis, Leandros; Geras-Raaka, Elizabeth; Varma, Anjali; Gershengorn, Marvin C.; Cesarman, Ethel
[Letter] Nature. 385(6614):347-350, January 23, 1997.

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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 [1,2] and in primary-effusion (body-cavity-based) lymphomas [3], malignancies that occur frequently, but not exclusively, in AIDS patients. KSHV is a gamma herpes-virus with homology to herpesvirus Saimiri and Epstein-Barr virus [1,4], both of which can transform lymphocytes [5]. Cloning of a KSHV genome fragment revealed the presence of an open reading frame encoding a putative G-protein-coupled receptor [6] that is homologous to a G-protein-coupled receptor encoded by herpesvirus Saimiri [7,8] and to human interleukin-8 receptors [9,10]. 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.

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