THE ROLE OF INTERFERON-BETA IN HUMAN CYTOMEGALOVIRUS-MEDIATED INHIBITION OF HLA DR INDUCTION ON ENDOTHELIAL-CELLS

Human cytomegalovirus (HCMV), a member of the virus family Herpesviridae that is associated with extensive worldwide morbidity and mortality in immunocompromised hosts, inhibits interferon-gamma (IFN gamma)-mediated induction of human leukocyte antigen (HLA) class II antigens on endothelial cells. In this study, the ability of HCMV-infected endothelial cells to synthesize interferon-beta (IFN beta), and the role of IFN beta in HCMV-mediated inhibition of HLA class II induction, was investigated. As detemined by an encephalomyocarditis virus protection assay, HCMV-infected endothelial cell culture supernatants contained 240 IU/ml of IFN type I activity, of which 99.9% was IFN beta, as compared to the absence of IFN beta in mock-infected culture supernatants. UV-irradiated supernatants from HCMV-infected cultures inhibited induction of HLA class II in noninfected cultures by 24%. This inhibition could be abolished with 500 NU/ml of anti-IFN beta antibody. Addition of anti-IFN beta antibody directly to HCMV-infected cultures mitigated but did not abolish HLA class II antigen inhibition. Dual immunohistochemistry for HCMV and HLA DR demonstrated that infected cells, in contrast to noninfected cells, were rarely induced to express HLA class II even in the presence of anti-IFN beta antibody. These findings suggest that HCMV inhibits induction of HLA class II antigens by IFN beta dependent and independent mechanisms.