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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.

SUBMITTER: Bridgeman A

PROVIDER: S-EPMC4617605 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Viruses transfer the antiviral second messenger cGAMP between cells.

Bridgeman A A Maelfait J J Davenne T T Partridge T T Peng Y Y Mayer A A Dong T T Kaever V V Borrow P P Rehwinkel J J

Science (New York, N.Y.) 20150730 6253

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 eff ...[more]

PMID: 26229117

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