Retinoic acid-inducible gene-I and interferon-beta promoter stimulator-1 augment proapoptotic responses following mammalian reovirus infection via interferon regulatory factor-3.
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.
Holm
Geoffrey H
GH
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2581, USA.
Zurney
Jennifer
J
Tumilasci
Vanessa
V
Leveille
Simon
S
Danthi
Pranav
P
Hiscott
John
J
Sherry
Barbara
B
Dermody
Terence S
TS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005347:Fibroblasts / Q000502:physiology; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000502:physiology*; D016899:Interferon-beta / Q000235:genetics*; D007668:Kidney; D051379:Mice; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic; D012088:Reoviridae Infections / Q000503:physiopathology*; D014162:Transfection
D050838:Interferon Regulatory Factor-3; D011971:Receptors, Immunologic; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases