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|Title:||Dengue virus activates cGAS through the release of mitochondrial DNA||Authors:||Sun B.
MB21D1 protein, human
growth, development and aging
|Issue Date:||2017||Citation:||Sun B., Sundström K.B., Chew J.J., Bist P., Gan E.S., Tan H.C., Goh K.C., Chawla T., Tang C.K., Ooi E.E. (2017). Dengue virus activates cGAS through the release of mitochondrial DNA. Scientific Reports 7 (1) : 3594. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-03932-1||Abstract:||Cyclic GMP-AMP synthetase (cGAS) is a DNA-specific cytosolic sensor, which detects and initiates host defense responses against microbial DNA. It is thus curious that a recent study identified cGAS as playing important roles in inhibiting positive-sense single-stranded RNA (+ssRNA) viral infection, especially since RNA is not known to activate cGAS. Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53), we show that infection creates an endogenous source of cytosolic DNA in infected cells through the release of mitochondrial DNA (mtDNA) to drive the production of cGAMP by cGAS. Innate immune responses triggered by cGAMP contribute to limiting the spread of DENV to adjacent uninfected cells through contact dependent gap junctions. Our result thus supports the notion that RNA virus indirectly activates a DNA-specific innate immune signaling pathway and highlights the breadth of the cGAS-induced antiviral response. © 2017 The Author(s).||Source Title:||Scientific Reports||URI:||https://scholarbank.nus.edu.sg/handle/10635/175184||ISSN:||20452322||DOI:||10.1038/s41598-017-03932-1|
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