Synergistic activation of interferon-beta gene transcription by the viral FLICE inhibitory protein of Kaposi's sarcoma-associated herpesvirus and type I IFN activators.
Expression of Kaposi's sarcoma-associated herpesvirus v-FLIP leads to the spindle-shape morphology of endothelial cells and is essential for the survival of primary effusion lymphoma cells. Activation of the NF-kappaB transcription factor by v-FLIP is responsible for these effects. Considering that the interferon-beta (ifn-beta) gene is regulated partly through NF-kappaB, we sought to determine whether v-FLIP would activate the expression of the ifn-beta gene. Our results indicate that when v-FLIP is expressed by itself it has no effect on ifn-beta gene activation but when it is combined with known IFN-beta inducers, a synergistic activation of the ifn-beta gene occurs. This effect is strictly dependent on NF-kappaB and is mediated through the positive regulatory domain II of the IFN-beta promoter. Furthermore, we report that protection from Fas-induced cell-death by v-FLIP is observed whether or not the type I IFN signaling pathway is activated. Our work therefore contributes to increase our knowledge on v-FLIP, highlighting the complex immunomodulatory properties of this anti-apoptotic viral protein.
Cloutier
Nathalie
N
Laboratory of Virology, Rheumatology and Immunology Research Center, CHUL Research Center and Faculty of Medicine, Laval University, Quebec, Canada.
Grandvaux
Nathalie
N
Flamand
Louis
L
D000276:Adjuvants, Immunologic / Q000502:physiology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000502:physiology*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology*; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D007370:Interferon Type I / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000821:virology; D029082:Sendai virus / Q000502:physiology; D015533:Transcriptional Activation
D000276:Adjuvants, Immunologic; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D007369:Interferon Inducers; D007370:Interferon Type I; D016899:Interferon-beta