Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation

Nature. 1997 Jan 23;385(6614):347-50. doi: 10.1038/385347a0.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Binding, Competitive
  • COS Cells
  • Cell Division
  • Cell Line
  • Cell Transformation, Viral
  • Chemokines / metabolism
  • Cloning, Molecular
  • GTP-Binding Proteins / metabolism*
  • Herpesvirus 8, Human / genetics*
  • Humans
  • Inositol Phosphates / metabolism
  • Interleukin-8 / metabolism*
  • Luciferases / genetics
  • Rats
  • Receptors, Cytokine / genetics*
  • Receptors, Cytokine / metabolism
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-8A
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sarcoma, Kaposi / virology
  • Second Messenger Systems
  • Signal Transduction
  • Transcription, Genetic
  • Transfection
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • Antigens, CD
  • Chemokines
  • Inositol Phosphates
  • Interleukin-8
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-8A
  • Receptors, Virus
  • Recombinant Proteins
  • Viral Proteins
  • Luciferases
  • GTP-Binding Proteins