Viruses transfer the antiviral second messenger cGAMP between cells

  • Science. 2015 Sep 11;349(6253):1228-32. doi: 10.1126/science.aab3632.
A Bridgeman  1 ,  J Maelfait  1 ,  T Davenne  1 ,  T Partridge  2 ,  Y Peng  1 ,  A Mayer  1 ,  T Dong  1 ,  V Kaever  3 ,  P Borrow  2 ,  J Rehwinkel  4
Affiliations
  • 1. Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • 2. Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
  • 3. Research Core Unit Metabolomics, Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
  • 4. Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. [email protected].
PMID: 26229117 DOI: 10.1126/science.aab3632
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.