Rotavirus-induced IFN-β promotes anti-viral signaling and apoptosis that modulate viral replication in intestinal epithelial cells

Amena H. Frias, Rheinallt M. Jones, Nimita H. Fifadara, Matam Vijay-Kumar, Andrew T. Gewirtz

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Rotavirus (RV), a leading cause of diarrhea, primarily infects intestinal epithelial cells (IEC). Rotavirus-infected IEC produce IFN-β and express hundreds of IFN-dependent genes. We thus hypothesized that type 1 IFN plays a key role in helping IEC limit RV replication and/or protect against cell death. To test this hypothesis, we examined IEC (HT29 cells) infected with RV (MOI 1) ± neutralizing antibodies to IFN-α/β via microscopy and SDS-PAGE immunoblotting. We hypothesized that neutralization of IFN would be clearly detrimental to RV-infected IEC. Rather, we observed that blockade of IFN function rescued IEC from the apoptotic cell death that otherwise would have occurred 24-48 h following exposure to RV. This resistance to cell death correlated with reduced levels of viral replication at early time points (< 8 h) following infection and eventuated in reduced production of virions. The reduction in RV replication that resulted from IFN neutralization correlated with, and could be recapitulated by, blockade of IFN-induced protein kinase R (PKR) activation, suggesting involvement of this kinase. Interestingly, pharmacologic blockade of caspase activity ablated RV-induced apoptosis and dramatically increased viral protein synthesis, suggesting that IFN-induced apoptosis helps to control RV infection. These results suggest non-mutually exclusive possibilities that IFN signaling is usurped by RV to promote early replication and induction of cell death may be a means by which IFN signaling possibly clears RV from the intestine.

Original languageEnglish (US)
Pages (from-to)294-306
Number of pages13
JournalInnate Immunity
Volume18
Issue number2
DOIs
StatePublished - Apr 1 2012

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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