Organ-specific roles for transcription factor NF-κB in reovirus-induced apoptosis and disease
Sean M. O’Donnell, … , Barbara Sherry, Terence S. Dermody
Sean M. O’Donnell, … , Barbara Sherry, Terence S. Dermody
Published September 1, 2005
Citation Information: J Clin Invest. 2005;115(9):2341-2350. https://doi.org/10.1172/JCI22428.
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Research Article Virology

Organ-specific roles for transcription factor NF-κB in reovirus-induced apoptosis and disease

Abstract

Reovirus induces apoptosis in cultured cells and in vivo. In cell culture models, apoptosis is contingent upon a mechanism involving reovirus-induced activation of transcription factor NF-κB complexes containing p50 and p65/RelA subunits. To explore the in vivo role of NF-κB in this process, we tested the capacity of reovirus to induce apoptosis in mice lacking a functional nfkb1/p50 gene. The genetic defect had no apparent effect on reovirus replication in the intestine or dissemination to secondary sites of infection. In comparison to what was observed in wild-type controls, apoptosis was significantly diminished in the CNS of p50-null mice following reovirus infection. In sharp contrast, the loss of p50 was associated with massive reovirus-induced apoptosis and uncontrolled reovirus replication in the heart. Levels of IFN-β mRNA were markedly increased in the hearts of wild-type animals but not p50-null animals infected with reovirus. Treatment of p50-null mice with IFN-β substantially diminished reovirus replication and apoptosis, which suggests that IFN-β induction by NF-κB protects against reovirus-induced myocarditis. These findings reveal an organ-specific role for NF-κB in the regulation of reovirus-induced apoptosis, which modulates encephalitis and myocarditis associated with reovirus infection.

Authors

Sean M. O’Donnell, Mark W. Hansberger, Jodi L. Connolly, James D. Chappell, Melissa J. Watson, Janene M. Pierce, J. Denise Wetzel, Wei Han, Erik S. Barton, J. Craig Forrest, Tibor Valyi-Nagy, Fiona E. Yull, Timothy S. Blackwell, Jeffrey N. Rottman, Barbara Sherry, Terence S. Dermody

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Figure 1

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NF-κB activation following reovirus infection of HLL mice. Newborn HLL m...
NF-κB activation following reovirus infection of HLL mice. Newborn HLL mice were inoculated perorally with PBS (A) or 104 PFU reovirus T3SA+ (B). Mice were inoculated intraperitoneally with luciferin 7 days after infection and imaged for luciferase activity as a marker for NF-κB activation. Bioluminescence indicates areas of NF-κB activation.