Increase in the Expression of Human Leukocyte Antigen Class I in Human Fibroblasts by Soluble Factors Secreted from Human Cytomegalovirus-infected Cells

The human cytomegalovirus (HCMV) is known to downregulate the expression of the human leukocyte antigen (HLA) class I for escape from immune surveillance. In order to understand the HCMV immune evasion mechanism, expression of HLA class I on the surface of HCMV-infected cells was investigated. A decrease in the HLA class I expression was observed at higher MOI; whereas at a lower MOI a slight increase in the HLA class I expression was observed. When HCMV-infected and uninfected cells were separately prepared on coverslips and co-cultured, the increased HLA class I expression was observed in uninfected cells. Treatment of the uninfected cells with the culture supernatant from HCMV-infected cells resulted in an increase in the HLA class I expression. A biochemical analysis of the HCMV-infected cell culture supernatant revealed the presence of interferon (IFN) β□, interleukin (IL)-1β, and IL-6. The HLA class I- enhancing activity of the culture supernatant was mimicked by IFN β, but not by IL1-β or IL-6, and was partially reversed by pretreatment with an antibody to IFN β. Therefore, it appears that the HCMV infection of human foreskin fibroblast cells induces interferon β and other soluble factor(s) that are responsible for the up-regulation of the HLA class I expression.