title: Organ-specific roles for transcription factor NF-kappaB 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-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.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: O'Donnell
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hansberger
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Connolly
authors.forename: James D
authors.initials: JD
authors.lastname: Chappell
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Watson
authors.forename: Janene M
authors.initials: JM
authors.lastname: Pierce
authors.forename: J Denise
authors.initials: JD
authors.lastname: Wetzel
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Erik S
authors.initials: ES
authors.lastname: Barton
authors.forename: J Craig
authors.initials: JC
authors.lastname: Forrest
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Yull
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Rottman
authors.forename: Barbara
authors.initials: B
authors.lastname: Sherry
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D006321:Heart / Q000821:virology; D020287:In Situ Nick-End Labeling; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D012087:Reoviridae / Q000235:genetics / Q000502:physiology*; D012088:Reoviridae Infections / Q000378:metabolism / Q000473:pathology; D014779:Virus Replication
chemical_list: D052002:NF-kappa B p50 Subunit; D016899:Interferon-beta