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

J Clin Invest. 2005 Sep;115(9):2341-50. doi: 10.1172/JCI22428. Epub 2005 Aug 11.


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-kappaB complexes containing p50 and p65/RelA subunits. To explore the in vivo role of NF-kappaB 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-beta 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-beta substantially diminished reovirus replication and apoptosis, which suggests that IFN-beta induction by NF-kappaB protects against reovirus-induced myocarditis. These findings reveal an organ-specific role for NF-kappaB in the regulation of reovirus-induced apoptosis, which modulates encephalitis and myocarditis associated with reovirus infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / physiology*
  • Brain / cytology
  • Brain / metabolism
  • Brain / virology
  • Cell Line
  • Heart / virology
  • In Situ Nick-End Labeling
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Intestines / virology
  • Mice
  • Mice, Knockout
  • Myocarditis / pathology
  • Myocarditis / virology
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism*
  • Reoviridae / genetics
  • Reoviridae / physiology*
  • Reoviridae Infections* / metabolism
  • Reoviridae Infections* / pathology
  • Virus Replication


  • NF-kappa B p50 Subunit
  • Interferon-beta