Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human monocytes: implications for immune evasion by EBV.
AffiliationDepartment of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester, M20 9BX United Kingdom. email@example.com
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AbstractMonocytes and macrophages play a central role in viral infections, as a target for viruses and in activation of both innate and adaptive immune responses. Epstein-Barr virus (EBV) has evolved elaborate strategies to dampen the immune system and to persist within the host. There is evidence that the product of the BCRF-1 open reading frame of EBV, viral interleukin-10 (vIL-10), inhibits the capacity of monocytes/macrophages to induce T cell activation, but the full mechanism of this effect is unknown. To determine whether this effect might involve modulation of the expression of accessory molecules known to be important in T cell activation, we analyzed by flow cytometry the influence of vIL-10 on the basal as well as on IFN-gamma-induced up-regulation of HLA molecules, ICAM-1, and two members of the B7 family B7.1 (CD80) and B7.2 (CD86) at the surface of human monocytes. Viral IL-10 in a concentration-dependent manner inhibited both basal- and IFN-gamma-induced HLA-class II, ICAM-1 (basal levels of ICAM-2 and ICAM-3 is unaffected), CD80, and CD86 up-regulation when added simultaneously with IFN-gamma. In contrast, complete inhibition of HLA-class I expression on monocytes/macrophages occurred only when vIL-10 was present 2 h prior to the addition of IFN-gamma, implying that vIL-10 affects an early step in the IFN-gamma signaling pathway. As both monocytes and macrophages can be infected by EBV, we propose that vIL-10-mediated impairment of monocyte/macrophage antigen-presenting function could help the virus-infected cells to avoid detection by the host's T cells on one hand and contribute to its immunosuppressive properties on the other.
CitationEpstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human monocytes: implications for immune evasion by EBV. 2002, 304 (2):342-51 Virology