An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication

Mol Cell. 2018 Sep 6;71(5):825-840.e6. doi: 10.1016/j.molcel.2018.07.009. Epub 2018 Aug 9.


Virulent pathogens often cause the release of host-derived damage-associated molecular patterns (DAMPs) from infected cells. During encounters with immune-evasive viruses that block inflammatory gene expression, preformed DAMPs provide backup inflammatory signals that ensure protective immunity. Whether DAMPs exhibit additional backup defense activities is unknown. Herein, we report that viral infection of barrier epithelia (keratinocytes) elicits the release of preformed interleukin-1 (IL-1) family cytokines, including the DAMP IL-1α. Mechanistic studies revealed that IL-1 acts on skin fibroblasts to induce an interferon (IFN)-like state that restricts viral replication. We identified a branch in the IL-1 signaling pathway that induces IFN-stimulated gene expression in infected cells and found that IL-1 signaling is necessary to restrict viral replication in human skin explants. These activities are most important to control immune-evasive virus replication in fibroblasts and other barrier cell types. These findings highlight IL-1 as an important backup antiviral system to ensure barrier defense.

Keywords: IRF1; ISGs; antiviral defense; innate immunity; interferon regulatory factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Female
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Gene Expression / immunology
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immune Evasion / immunology*
  • Interleukin-1 / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / immunology*
  • Skin / immunology
  • Skin / virology
  • Vero Cells
  • Virus Replication / immunology*


  • Interleukin-1