Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection

Daniel Rubio, Ren Huan Xu, Sanda Remakus, Tracy E. Krouse, Mary Ellen Truckenmiller, Roshan J. Thapa, Siddharth Balachandran, Antonio Alcamí, Christopher C. Norbury, Luis J. Sigal

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45 Scopus citations

Abstract

Nuclear factor kappa B (NF-κB) and type 1 interferon (T1-IFN) signaling are innate immune mechanisms activated upon viral infection. However, the role of NF-κB and its interplay with T1-IFN in antiviral immunity is poorly understood. We show that NF-κB is essential for resistance to ectromelia virus (ECTV), a mouse orthopoxvirus related to the virus causing human smallpox. Additionally, an ECTV mutant lacking an NF-κB inhibitor activates NF-κB more effectively in vivo, resulting in increased proinflammatory molecule transcription in uninfected cells and organs and decreased viral replication. Unexpectedly, NF-κB activation compensates for genetic defects in the T1-IFN pathway, such as a deficiency in the IRF7 transcription factor, resulting in virus control. Thus, overlap between the T1-IFN and NF-κB pathways allows the host to overcome genetic or pathogen-induced deficiencies in T1-IFN and survive an otherwise lethal poxvirus infection. These findings may also explain why some pathogens target both pathways to cause disease.

Original languageEnglish (US)
Pages (from-to)701-710
Number of pages10
JournalCell Host and Microbe
Volume13
Issue number6
DOIs
StatePublished - Jun 12 2013

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Cite this

Rubio, D., Xu, R. H., Remakus, S., Krouse, T. E., Truckenmiller, M. E., Thapa, R. J., Balachandran, S., Alcamí, A., Norbury, C. C., & Sigal, L. J. (2013). Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection. Cell Host and Microbe, 13(6), 701-710. https://doi.org/10.1016/j.chom.2013.04.015