How to Inhibit Nuclear Factor-Kappa B Signaling: Lessons from Poxviruses

Joshua B. Reus, Emily A. Rex, Don B. Gammon

Research output: Contribution to journalReview articlepeer-review


The Nuclear Factor-kappa B (NF-κB) family of transcription factors regulates key host inflammatory and antiviral gene expression programs, and thus, is often activated during viral infection through the action of pattern-recognition receptors and cytokine–receptor interactions. In turn, many viral pathogens encode strategies to manipulate and/or inhibit NF-κB signaling. This is particularly exemplified by vaccinia virus (VV), the prototypic poxvirus, which encodes at least 18 different inhibitors of NF-κB signaling. While many of these poxviral NF-κB inhibitors are not required for VV replication in cell culture, they virtually all modulate VV virulence in animal models, underscoring the important influence of poxvirus–NF-κB pathway interactions on viral pathogenesis. Here, we review the diversity of mechanisms through which VV-encoded antagonists inhibit initial NF-κB pathway activation and NF-κB signaling intermediates, as well as the activation and function of NF-κB transcription factor complexes.

Original languageEnglish (US)
Article number1061
Issue number9
StatePublished - Sep 2022


  • NF-κB pathway
  • immune evasion
  • innate immunity
  • poxvirus
  • vaccinia virus
  • virus–host interactions

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases


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