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

Christian K. Holm, Søren B. Jensen, Martin R. Jakobsen, Natalia Cheshenko, Kristy A. Horan, Hanne B. Moeller, Regina Gonzalez-Dosal, Simon B. Rasmussen, Maria H. Christensen, Timur O. Yarovinsky, Frazer J. Rixon, Betsy C. Herold, Katherine A. Fitzgerald, Søren R. Paludan

Research output: Contribution to journalArticle

128 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)737-743
Number of pages7
JournalNature Immunology
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Holm, C. K., Jensen, S. B., Jakobsen, M. R., Cheshenko, N., Horan, K. A., Moeller, H. B., Gonzalez-Dosal, R., Rasmussen, S. B., Christensen, M. H., Yarovinsky, T. O., Rixon, F. J., Herold, B. C., Fitzgerald, K. A., & Paludan, S. R. (2012). Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nature Immunology, 13(8), 737-743. https://doi.org/10.1038/ni.2350