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

Lisa M. Sedger*, Donna M. Shows, Rebecca A. Blanton, Jacques J. Peschon, Ray G. Goodwin, David Cosman, Steven R. Wiley

*Corresponding author for this work

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is able to kill many transformed cells of diverse tissue types. We show that TRAIL is inducible by IFN-γ, by TNF-α, and by infection with human CMV, and has potent antiviral activity in vitro. CMV infection and IFN-γ also reciprocally modulate TRAIL receptor (TRAIL-R) expression. CMV infection increased the expression of TRA IL-R1 and -R2, whereas IFN-γ down-regulated the expression of TRAIL-Rs on uninfected fibroblasts. Moreover, IFN-γ significantly decreased the basal level of NF-κB activation, a known survival factor that inhibits apoptosis. Thus, TRAIL selectively kills virus-infected cells while leaving uninfected cells intact, and IFN-γ 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.

Original languageEnglish
Pages (from-to)920-926
Number of pages7
JournalJournal of Immunology
Volume163
Issue number2
Publication statusPublished - 15 Jul 1999

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