Retinoic acid-inducible gene-I and interferon-beta promoter stimulator-1 augment proapoptotic responses following mammalian reovirus infection via interferon regulatory factor-3.

Holm GH, Zurney J, Tumilasci V, Leveille S, Danthi P, Hiscott J, Sherry B, Dermody TS
J Biol Chem. 2007 282 (30): 21953-61

PMID: 17540767 · DOI:10.1074/jbc.M702112200

During viral infection, cells initiate antiviral responses to contain replication and inhibit virus spread. One protective mechanism involves activation of transcription factors interferon regulatory factor-3 (IRF-3) and NF-kappaB, resulting in secretion of the antiviral cytokine, interferon-beta. Another is induction of apoptosis, killing the host cell before virus disseminates. Mammalian reovirus induces both interferon-beta and apoptosis, raising the possibility that both pathways are initiated by a common cellular sensor. We show here that reovirus activates IRF-3 with kinetics that parallel the activation of NF-kappaB, a known mediator of reovirus-induced apoptosis. Activation of IRF-3 requires functional retinoic acid inducible gene-I and interferon-beta promoter stimulator-1, but these intracellular sensors are dispensable for activation of NF-kappaB. Interferon-beta promoter stimulator-1 and IRF-3 are required for efficient apoptosis following reovirus infection, suggesting a common mechanism of antiviral cytokine induction and activation of the cell death response.

MeSH Terms (16)

Animals Apoptosis Cell Line DEAD-box RNA Helicases DEAD Box Protein 58 Fibroblasts Genes, Reporter HeLa Cells Humans Interferon-beta Interferon Regulatory Factor-3 Kidney Mice Promoter Regions, Genetic Reoviridae Infections Transfection

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