Varicella-zoster virus infection triggers formation of an interleukin-1β (IL-1β)-processing inflammasome complex

J Biol Chem. 2011 May 20;286(20):17921-33. doi: 10.1074/jbc.M110.210575. Epub 2011 Mar 8.


Innate cellular immunity is the immediate host response against pathogens, and activation of innate immunity also modulates the induction of adaptive immunity. The nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a family of intracellular receptors that recognize conserved patterns associated with intracellular pathogens, but information about their role in the host defense against DNA viruses is limited. Here we report that varicella-zoster virus (VZV), an alphaherpesvirus that is the causative agent of varicella and herpes zoster, induces formation of the NLRP3 inflammasome and the associated processing of the proinflammatory cytokine IL-1β by activated caspase-1 in infected cells. NLRP3 inflammasome formation was induced in VZV-infected human THP-1 cells, which are a transformed monocyte cell line, primary lung fibroblasts, and melanoma cells. Absent in melanoma gene-2 (AIM2) is an interferon-inducible protein that can form an alternative inflammasome complex with caspase-1 in virus-infected cells. Experiments in VZV-infected melanoma cells showed that NLRP3 protein recruits the adaptor protein ASC and caspase-1 to form an NLRP3 inflammasome complex independent of AIM2 protein and in the absence of free radical reactive oxygen species release. NLRP3 was also expressed extensively in infected skin xenografts in the severe combined immunodeficiency mouse model of VZV pathogenesis in vivo. We conclude that NLRP3 inflammasome formation is an innate cellular response to infection with this common pathogenic human herpesvirus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Caspase 1 / genetics
  • Caspase 1 / immunology
  • Caspase 1 / metabolism
  • Cell Line, Tumor
  • Chickenpox / genetics
  • Chickenpox / immunology
  • Chickenpox / metabolism*
  • DNA-Binding Proteins
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • Herpes Zoster / genetics
  • Herpes Zoster / immunology
  • Herpes Zoster / metabolism*
  • Herpesvirus 3, Human / immunology
  • Herpesvirus 3, Human / metabolism*
  • Humans
  • Immunity, Innate*
  • Inflammasomes / genetics
  • Inflammasomes / immunology
  • Inflammasomes / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism*
  • Mice
  • Mice, SCID
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism
  • Skin Transplantation
  • Transplantation, Heterologous


  • AIM2 protein, human
  • Aim2 protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nlrp3 protein, mouse
  • Nuclear Proteins
  • Caspase 1