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 Norbury, Luis J. Sigal

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

Fingerprint

Interferon Type I
NF-kappa B
Virus Diseases
Ectromelia virus
Poxviridae Infections
Orthopoxvirus
Viruses
Smallpox
Antiviral Agents
Immunity
Transcription Factors

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., ... 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
Rubio, Daniel ; Xu, Ren Huan ; Remakus, Sanda ; Krouse, Tracy E. ; Truckenmiller, Mary Ellen ; Thapa, Roshan J. ; Balachandran, Siddharth ; Alcamí, Antonio ; Norbury, Christopher ; Sigal, Luis J. / Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection. In: Cell Host and Microbe. 2013 ; Vol. 13, No. 6. pp. 701-710.
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Rubio, D, Xu, RH, Remakus, S, Krouse, TE, Truckenmiller, ME, Thapa, RJ, Balachandran, S, Alcamí, A, Norbury, C & Sigal, LJ 2013, 'Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection', Cell Host and Microbe, vol. 13, no. 6, pp. 701-710. https://doi.org/10.1016/j.chom.2013.04.015

Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection. / Rubio, Daniel; Xu, Ren Huan; Remakus, Sanda; Krouse, Tracy E.; Truckenmiller, Mary Ellen; Thapa, Roshan J.; Balachandran, Siddharth; Alcamí, Antonio; Norbury, Christopher; Sigal, Luis J.

In: Cell Host and Microbe, Vol. 13, No. 6, 12.06.2013, p. 701-710.

Research output: Contribution to journalArticle

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AU - Sigal, Luis J.

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