Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING.
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.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Christian K
CK
Holm
Søren B
SB
Jensen
Martin R
MR
Jakobsen
Natalia
N
Cheshenko
Kristy A
KA
Horan
Hanne B
HB
Moeller
Regina
R
Gonzalez-Dosal
Simon B
SB
Rasmussen
Maria H
MH
Christensen
Timur O
TO
Yarovinsky
Frazer J
FJ
Rixon
Betsy C
BC
Herold
Katherine A
KA
Fitzgerald
Søren R
SR
Paludan
D000818:Animals; D002459:Cell Fusion; D054357:Chemokine CXCL10 / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D053586:Virus Internalization; D000099197:STING Protein
D054357:Chemokine CXCL10; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C485433:Cxcl10 protein, mouse; C507780:Myd88 protein, mouse; C532857:STING1 protein, human; D000099197:STING Protein; C530855:Sting1 protein, mouse; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse