Randolph-Habecker Julie-Randoph, Rahill Brian, Torok-Storb Beverly, Vieira Jeffrey, Kolattukudy Pappachan E, Rovin Brad H, Sedmak Daniel D
Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA.
Cytokine. 2002 Jul 7;19(1):37-46. doi: 10.1006/cyto.2002.0874.
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.
我们推测，巨细胞病毒（CMV）的CC趋化因子受体同系物US28在调节宿主抗病毒防御中发挥作用。由于内源性产生的CC趋化因子MCP-1和RANTES，来自感染CMV的US28缺失突变体（CMV ΔUS28）的成纤维细胞的上清液可诱导单核细胞趋化性。然而，这些趋化因子从确实表达US28的CMV感染细胞的上清液中被隔离。US28也能够隔离外源性添加的RANTES。令人惊讶的是，与CMV感染的细胞相比，感染CMV ΔUS28的细胞转录并分泌了更高水平的IL-8（一种CXC趋化因子）。最后，由于趋化因子是免疫细胞通过内皮迁移的有效介质，我们对CMV感染的内皮细胞的CC趋化因子结合潜力进行了表征。我们提出，US28通过隔离内源性和外源性产生的趋化因子而作为一个“趋化因子池”发挥作用，并改变CXC趋化因子IL-8的产生，这表明CMV可显著改变感染细胞周围的炎症环境。
