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

J Clin Invest. 1998 Oct 15;102(8):1469-72. doi: 10.1172/JCI4461.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Receptors, Chemokine / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction

Substances

  • 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