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

Publication Type:

Journal Article

Source:

Cytokine, Volume 19, Issue 1, p.37-46 (2002)

Keywords:

Blotting, Northern, Cells, Cultured, Chemokine CCL5, CHEMOKINES, Chemokines, CC, Chemotaxis, CYTOMEGALOVIRUS, Dose-Response Relationship, Drug, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Humans, INFLAMMATION, Interleukin-8, Monocytes, Protein Binding, Receptors, Chemokine, Reverse Transcriptase Polymerase Chain Reaction, Umbilical Veins, Viral Proteins

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.