title: Viruses transfer the antiviral second messenger cGAMP between cells.
abstract: Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bridgeman
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: J
authors.initials: J
authors.lastname: Maelfait
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: T
authors.initials: T
authors.lastname: Davenne
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
authors.forename: T
authors.initials: T
authors.lastname: Partridge
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: A
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: T
authors.initials: T
authors.lastname: Dong
authors.affiliation: Research Core Unit Metabolomics, Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
authors.forename: P
authors.initials: P
authors.lastname: Borrow
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. jan.rehwinkel@imm.ox.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Rehwinkel
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015290:Second Messenger Systems; D015533:Transcriptional Activation; D014771:Virion / Q000235:genetics / Q000378:metabolism*
chemical_list: D016915:AIDS Vaccines; D022301:Herpes Simplex Virus Vaccines; D009712:Nucleotides, Cyclic; C584311:cyclic guanosine monophosphate-adenosine monophosphate; D016899:Interferon-beta