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Transmission of innate immune signaling by packaging of cGAMP in viral particles.

Authors
  • Gentili, Matteo1
  • Kowal, Joanna1
  • Tkach, Mercedes1
  • Satoh, Takeshi1
  • Lahaye, Xavier1
  • Conrad, Cécile1
  • Boyron, Marilyn2
  • Lombard, Bérangère3
  • Durand, Sylvère4
  • Kroemer, Guido5
  • Loew, Damarys3
  • Dalod, Marc2
  • Théry, Clotilde6
  • Manel, Nicolas7
  • 1 INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France. , (France)
  • 2 Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM U1104, CNRS UMR7280, 13288 Marseille, France. , (France)
  • 3 Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, Paris, France. , (France)
  • 4 Labex Dendritic Cell Biology (DCBIOL), Paris, France. , (France)
  • 5 Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France. , (France)
  • 6 INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France. Labex Dendritic Cell Biology (DCBIOL), Paris, France. , (France)
  • 7 INSERM U932, Immunity and Cancer Unit, Institut Curie, Paris, France. Labex Dendritic Cell Biology (DCBIOL), Paris, France. Labex Vaccine Research Institute (VRI), Paris, France. [email protected] , (France)
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Sep 11, 2015
Volume
349
Issue
6253
Pages
1232–1236
Identifiers
DOI: 10.1126/science.aab3628
PMID: 26229115
Source
Medline
Language
English
License
Unknown

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. Copyright © 2015, American Association for the Advancement of Science.

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