title: Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human monocytes: implications for immune evasion by EBV.
abstract: Monocytes 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.
authors.affiliation: Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester, M20 9BX United Kingdom. ssalek@liai.org
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.forename: John R
authors.initials: JR
authors.lastname: Arrand
authors.forename: Mike
authors.initials: M
authors.lastname: Mackett
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000633:toxicity*; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects*; D014764:Viral Proteins / Q000633:toxicity*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D014764:Viral Proteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma