Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; *Cell Fusion; Chemokine CXCL10; HEK293 Cells; HeLa Cells; Herpesvirus 1, Human; Humans; *Immunity, Innate; Interferon Type I; Leukocytes; Lymphocyte Activation; Macrophages; *Membrane Fusion; Membrane Glycoproteins; Membrane Proteins; Mice; Mice, Knockout; Myeloid Differentiation Factor 88; Signal Transduction; Toll-Like Receptor 7; Toll-Like Receptor 9; Virus Internalization
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.
Holm, Christian K.; Jensen, Soren B.; Jakobsen, Martin R.; Cheshenko, Natalia; Horan, Kristy A.; Moeller, Hanne B.; Gonzalez-Dosal, Regina; Rasmussen, Simon B.; Christensen, Maria H.; Yarovinsky, Timur O.; Rixon, Frazer J.; Herold, Betsy C.; Fitzgerald, Katherine A.; and Paludan, Soren R., "Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING" (2012). Infectious Diseases and Immunology Publications and Presentations. 145.