Effect of cmvIL-10 on human CXC-receptor 4 signaling

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that establishes lifelong latency. HCMV uses viral proteins that imitate host signaling pathways. The HCMV gene UL111A encodes cmvIL-10, a homolog of human interleukin-10 (IL-10). IL-10 is an antiinflammatory cytokine with immunosuppressive functions. CmvIL-10 shares many of these functions, including enhancing signaling outcomes from human chemokine receptor CXCR4 towards its known ligand CXCL12. CXCL12/CXCR4 signaling is essential for developmental processes. CXCR4 has another natural ligand, extracellular ubiquitin (Ub), exerting a range of effects on immune responses and anti-inflammatory activities. To investigate whether cmvIL-10 augments signaling outcomes from Ub binding to CXCR4, human embryonic kidney (HEK-293) cells were treated with Ub in the presence or absence of cmvIL-10. Cell proliferation and migration were monitored using the Incucyte Live Cell Analysis System. Our results will determine if cmvIL-10 exerts control over Ub/CXCR4 pathway and will help clarify the immunomodulatory effects of HCMV on the host cell.