Abstract:
TNF-related apoptosis-inducing ligand (TRAIL) is able to kill many transformed cells of diverse tissue types, We low that TRAIL is inducible by IFN-gamma, by TNF-alpha, and by infection with human CMV, and has potent antiviral activity in vitro, CMV infection and IFN-gamma also reciprocally modulate TRAIL receptor (TRAIL-R) expression. CMV infection increased the expression of TRAIL-R1 and -R2, whereas IFN-gamma down-regulated the expression of TRAIL-Rs on uninfected fibroblasts, Moreover, IFN-gamma significantly decreased the basal level of NF-kappa B activation, a known survival factor that inhibits apoptosis, Thus, TRAIL selectively kills virus-infected cells while leaving uninfected cells intact, and IFN-gamma potentiates these effects by dynamic modulation of TRAIL and TRAIL-R expression and by sensitizing cells to apoptosis, The regulation of TRAIL and TRAIL-R expression may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis.
