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Viruses transfer the antiviral second messenger cGAMP between cells

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Science  11 Sep 2015:
Vol. 349, Issue 6253, pp. 1228-1232
DOI: 10.1126/science.aab3632

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Viruses pack antiviral mediators

Viruses often hijack host proteins for their own use, turning host cells into virion-spewing machines. However, Bridgeman et al. and Gentili et al. now report a sneaky way that the host can fight back (see the Perspective by Schoggins). Host cells that expressed the enzyme cGAS, an innate immune receptor that senses cytoplasmic DNA, packaged the cGAS-generated second messenger cGAMP into virions. Virions could then transfer cGAMP to neighboring cells, triggering an antiviral gene program in these newly infected cells. Such transfer of an antiviral mediator may help to speed up the immune response to put the brakes on viral spread.

Science, this issue pp. 1228 and 1232; see also p. 1166

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.

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