IFN-gamma mediates a novel antiviral activity through dynamic modulation of TRAIL and TRAIL receptor expression

TNF-related apoptosis-inducing ligand (TRAIL) is able to kill many transfor med cells of diverse tissue types, We low that TRAIL is inducible by IFN-ga mma, by TNF-alpha, and by infection with human CMV, and has potent antivira l activity in vitro, CMV infection and IFN-gamma also reciprocally modulate TRAIL receptor (TRAIL-R) expression. CMV infection increased the expressio n of TRAIL-R1 and -R2, whereas IFN-gamma down-regulated the expression of T RAIL-Rs on uninfected fibroblasts, Moreover, IFN-gamma significantly decrea sed the basal level of NF-kappa B activation, a known survival factor that inhibits apoptosis, Thus, TRAIL selectively kills virus-infected cells whil e leaving uninfected cells intact, and IFN-gamma potentiates these effects by dynamic modulation of TRAIL and TRAIL-R expression and by sensitizing ce lls to apoptosis, The regulation of TRAIL and TRAIL-R expression may repres ent a general mechanism that contributes to the control of TRAIL-mediated a poptosis.