The expression of the cytomegalovirus chemokine receptor homolog US28 sequesters biologically active CC chemokines and alters IL-8 production.
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.
Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA.
Julie-Randoph
JR
Randolph-Habecker
Brian
B
Rahill
Beverly
B
Torok-Storb
Jeffrey
J
Vieira
Pappachan E
PE
Kolattukudy
Brad H
BH
Rovin
Daniel D
DD
Sedmak
D015152:Blotting, Northern; D002478:Cells, Cultured; D018946:Chemokine CCL5; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D002633:Chemotaxis; D003587:Cytomegalovirus / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D014764:Viral Proteins / Q000096:biosynthesis*
D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016209:Interleukin-8; D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins