Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING

Nat Immunol. 2012 Jun 17;13(8):737-43. doi: 10.1038/ni.2350.

Abstract

The innate immune system senses infection by detecting either evolutionarily conserved molecules essential for the survival of microbes or the abnormal location of molecules. Here we demonstrate the existence of a previously unknown innate detection mechanism induced by fusion between viral envelopes and target cells. Virus-cell fusion specifically stimulated a type I interferon response with expression of interferon-stimulated genes, in vivo recruitment of leukocytes and potentiation of signaling via Toll-like receptor 7 (TLR7) and TLR9. The fusion-dependent response was dependent on the stimulator of interferon genes STING but was independent of DNA, RNA and viral capsid. We suggest that membrane fusion is sensed as a danger signal with potential implications for defense against enveloped viruses and various conditions of giant-cell formation.

Publication types

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

MeSH terms

  • Animals
  • Cell Fusion*
  • Chemokine CXCL10 / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Immunity, Innate*
  • Interferon Type I / biosynthesis*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Lymphocyte Activation
  • Macrophages / metabolism
  • Membrane Fusion*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Signal Transduction
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / metabolism
  • Virus Internalization

Substances

  • Chemokine CXCL10
  • Cxcl10 protein, mouse
  • Interferon Type I
  • MPYS protein, mouse
  • Membrane Glycoproteins
  • Membrane Proteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • STING protein, human
  • Tlr7 protein, mouse
  • Tlr9 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9