Viruses transfer the antiviral second messenger cGAMP between cells.

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

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.

DOI

10.1126/science.aab3632

Type

Journal article

Journal

Science

Publication Date

11/09/2015

Volume

349

Pages

1228 - 1232

Keywords

AIDS Vaccines, Dendritic Cells, Genes, Reporter, Genetic Vectors, HEK293 Cells, HIV Infections, HIV-1, Herpes Simplex, Herpes Simplex Virus Vaccines, Herpesvirus 1, Human, Humans, Immunity, Innate, Interferon-beta, Nucleotides, Cyclic, Promoter Regions, Genetic, Second Messenger Systems, Transcriptional Activation, Virion

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