Publication Date:
2015-08-01
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617605/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617605/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bridgeman, A -- Maelfait, J -- Davenne, T -- Partridge, T -- Peng, Y -- Mayer, A -- Dong, T -- Kaever, V -- Borrow, P -- Rehwinkel, J -- 100954/Wellcome Trust/United Kingdom -- AI 114266/AI/NIAID NIH HHS/ -- MC_UU_12010/8/Medical Research Council/United Kingdom -- MR/K012037/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1228-32. doi: 10.1126/science.aab3632. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. ; Research Core Unit Metabolomics, Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. ; 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. jan.rehwinkel@imm.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229117" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/immunology
;
Dendritic Cells/immunology/virology
;
Genes, Reporter
;
Genetic Vectors/genetics/metabolism
;
HEK293 Cells
;
HIV Infections/*immunology/metabolism/prevention & control
;
HIV-1/genetics/*metabolism
;
Herpes Simplex/*immunology/prevention & control
;
Herpes Simplex Virus Vaccines/immunology
;
Herpesvirus 1, Human/genetics/*metabolism
;
Humans
;
Immunity, Innate/genetics/immunology
;
Interferon-beta/genetics/*immunology
;
Nucleotides, Cyclic/*metabolism
;
Promoter Regions, Genetic
;
*Second Messenger Systems
;
Transcriptional Activation
;
Virion/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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