The expression of the cytomegalovirus chemokine receptor homolog US28 sequesters biologically active CC chemokines and alters IL-8 production

Cytokine. 2002 Jul 7;19(1):37-46. doi: 10.1006/cyto.2002.0874.

Abstract

We hypothesized that US28, a cytomegalovirus (CMV) CC chemokine receptor homolog, plays a role in modulating the host antiviral defense. Monocyte chemotaxis was induced by supernatants from fibroblasts infected with a US28 deletion mutant of CMV (CMV Delta US28) due to endogenously produced CC chemokines MCP-1 and RANTES. However, these chemokines were sequestered from the supernatants of CMV-infected cells that did express US28. US28 was also capable of sequestering exogenously added RANTES. Surprisingly, cells infected with CMV Delta US28 transcribed and secreted increased levels IL-8, a CXC chemokine, when compared to CMV-infected cells. Finally, because chemokines are potent mediators of immune cell migration through the endothelium, we characterized the CC chemokine binding potential of CMV-infected endothelial cells. We propose that US28 functions as a 'chemokine sink' by sequestering endogenously and exogenously produced chemokines and alters the production of the CXC chemokine IL-8, suggesting that CMV could significantly alter the inflammatory milieu surrounding infected cells.

Publication types

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

MeSH terms

  • Blotting, Northern
  • Cells, Cultured
  • Chemokine CCL5
  • Chemokines / metabolism
  • Chemokines, CC / metabolism*
  • Chemotaxis
  • Cytomegalovirus / metabolism*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Inflammation
  • Interleukin-8 / metabolism*
  • Monocytes / cytology
  • Monocytes / immunology
  • Protein Binding
  • Receptors, Chemokine / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Umbilical Veins / cytology
  • Viral Proteins / biosynthesis*

Substances

  • Chemokine CCL5
  • Chemokines
  • Chemokines, CC
  • Interleukin-8
  • Receptors, Chemokine
  • US28 receptor, Cytomegalovirus
  • Viral Proteins