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Chemokines activate Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor in mammalian cells in culture.

Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8, a virus that appears to be involved in the pathogenesis of Kaposi's sarcoma and primary effusion lymphomas, encodes a G protein-coupled receptor (KSHV-GPCR) that exhibits constitutive signaling. In this report, we show that two chemokines, interleukin 8 (IL-8) and growth-related protein-alpha, activate KSHV-GPCR over constitutive levels. Moreover, as with human receptors, the integrity of the ELR motif of these chemokines is required for activation of KSHV-GPCR. Other residues that are required for IL-8 binding to human chemokine receptors CXCR1 and CXCR2 are important for KSHV-GPCR activation also. Thus, it appears that the ELR binding site and other key domains of ELR chemokine activation have been preserved in the virus KSHV-GPCR. The results suggest that KSHV-GPCR originated from CXCR1 or CXCR2 and that activation of KSHV-GPCR by endogenous chemokines may affect the pathobiology of KSHV infection in humans.
AuthorsM C Gershengorn, E Geras-Raaka, A Varma, I Clark-Lewis
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 102 Issue 8 Pg. 1469-72 (Oct 15 1998) ISSN: 0021-9738 [Print] United States
PMID9788958 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, mouse
  • G protein-coupled receptor, Human herpesvirus 8
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Oligopeptides
  • Receptors, Chemokine
  • Recombinant Proteins
  • Platelet Factor 4
  • GTP-Binding Proteins
Topics
  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokines (pharmacology)
  • Chemokines, CXC (pharmacology)
  • Chemotactic Factors (pharmacology)
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins (metabolism)
  • Growth Substances (pharmacology)
  • Herpesvirus 8, Human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8 (pharmacology)
  • Mice
  • Molecular Sequence Data
  • Oligopeptides (pharmacology)
  • Platelet Factor 4 (pharmacology)
  • Protein Binding
  • Receptors, Chemokine (genetics, metabolism)
  • Recombinant Proteins (metabolism)
  • Signal Transduction

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