Transmission of innate immune signaling by packaging of cGAMP in viral particles

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Science  30 Jul 2015:
DOI: 10.1126/science.aab3628

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Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic GMP-AMP synthase (cGAS) is a cytosolic sensor for many DNA viruses and HIV-1. In response to cytosolic viral DNA, cGAS synthesizes the second messenger 2′3′-cyclic GMP-AMP (cGAMP), which activates antiviral signaling pathways. We show that in cells producing virus, cGAS-synthesized cGAMP can be packaged in viral particles and extracellular vesicles. Viral particles efficiently delivered cGAMP to target cells. cGAMP transfer by viral particles to dendritic cells activated innate immunity and antiviral defenses. Finally, we show that cell-free murine cytomegalovirus and the attenuated human poxvirus vaccine Modified Vaccinia Ankara contained cGAMP. Thus transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells.

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