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.

Original publication

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