title: Transmission of innate immune signaling by packaging of cGAMP in viral particles.
abstract: Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a cytosolic sensor for many DNA viruses and HIV-1. In response to cytosolic viral DNA, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which activates antiviral signaling pathways. We show that in cells producing virus, cGAS-synthesized cGAMP can be packaged in viral particles and extracellular vesicles. Viral particles efficiently delivered cGAMP to target cells. cGAMP transfer by viral particles to dendritic cells activated innate immunity and antiviral defenses. Finally, we show that cell-free murine cytomegalovirus and Modified Vaccinia Ankara virus contained cGAMP. Thus, transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells.
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gentili
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kowal
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Tkach
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Lahaye
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM U1104, CNRS UMR7280, 13288 Marseille, France.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Boyron
authors.affiliation: Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, Paris, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Lombard
authors.affiliation: Labex Dendritic Cell Biology (DCBIOL), Paris, France.
authors.forename: Sylvère
authors.initials: S
authors.lastname: Durand
authors.affiliation: Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, Paris, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM U1104, CNRS UMR7280, 13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France. Labex Dendritic Cell Biology (DCBIOL), Paris, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Théry
authors.affiliation: INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France. Labex Dendritic Cell Biology (DCBIOL), Paris, France. Labex Vaccine Research Institute (VRI), Paris, France. nicolas.manel@curie.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Manel
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006566:Herpesviridae Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000235:genetics / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D015290:Second Messenger Systems; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D009712:Nucleotides, Cyclic; C584311:cyclic guanosine monophosphate-adenosine monophosphate