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Viruses transfer the antiviral second messenger cGAMP between cells.

Science (New York, N.Y.) | 2015

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.

Pubmed ID: 26229117 RIS Download

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/K012037/1
  • Agency: NIAID NIH HHS, United States
    Id: AI 114266
  • Agency: Wellcome Trust, United Kingdom
    Id: 100954
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI114266
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L018942/1
  • Agency: Medical Research Council, United Kingdom
    Id: G0600520
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12010/8
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K012037
  • Agency: Medical Research Council, United Kingdom
    Id: G1001046

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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