Reovirus-induced apoptosis requires activation of transcription factor NF-κB

Jodi L. Connolly, Steven Rodgers, Penny Clarke, Dean W. Ballard, Lawrence D. Kerr, Kenneth L. Tyler, Terence S. Dermody

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Abstract

Reovirus infection induces apoptosis in cultured cells and in vivo. To identify host cell factors that mediate this response, we investigated whether reovirus infection alters the activation state of the transcription factor nuclear factor kappa B (NF-κB). As determined in electrophoretic mobility shift assays, reovirus infection of HeLa cells leads to nuclear translocation of NF-κB complexes containing Rel family members p50 and p65. Reovirus-induced activation of NF-κB DNA-binding activity correlated with the onset of NF-κB-directed transcription in reporter gene assays. Three independent lines of evidence indicate that this functional form of NF-κB is required for reovirus-induced apoptosis. First, treatment of reovirus- infected HeLa cells with a proteasome inhibitor prevents NF-κB activation following infection and substantially diminishes reovirus-induced apoptosis. Second, transient expression of a dominant-negative form of IκB that constitutively represses NF-κB activation significantly reduces levels of apoptosis triggered by reovirus infection. Third, mutant cell lines deficient for either the p50 or p65 subunits of NF-κB are resistant to reovirus- induced apoptosis compared with cells expressing an intact NF-κB signaling pathway. These findings indicate that NF-κB plays a significant role in the mechanism by which reovirus induces apoptosis in susceptible host cells.

Original languageEnglish
Pages (from-to)2981-2989
Number of pages9
JournalJournal of Virology
Volume74
Issue number7
DOIs
StatePublished - Mar 22 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Connolly, J. L., Rodgers, S., Clarke, P., Ballard, D. W., Kerr, L. D., Tyler, K. L., & Dermody, T. S. (2000). Reovirus-induced apoptosis requires activation of transcription factor NF-κB. Journal of Virology, 74(7), 2981-2989. https://doi.org/10.1128/JVI.74.7.2981-2989.2000