Dengue virus activates cGAS through the release of mitochondrial DNA

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 in...

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Autores principales:	Bo Sun, Karin B. Sundström, Jun Jie Chew, Pradeep Bist, Esther S. Gan, Hwee Cheng Tan, Kenneth C. Goh, Tanu Chawla, Choon Kit Tang, Eng Eong Ooi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b41daa6c581143b7a27dd423f55e72bf
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spelling	oai:doaj.org-article:b41daa6c581143b7a27dd423f55e72bf2021-12-02T16:08:13ZDengue virus activates cGAS through the release of mitochondrial DNA10.1038/s41598-017-03932-12045-2322https://doaj.org/article/b41daa6c581143b7a27dd423f55e72bf2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03932-1https://doaj.org/toc/2045-2322Abstract 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.Bo SunKarin B. SundströmJun Jie ChewPradeep BistEsther S. GanHwee Cheng TanKenneth C. GohTanu ChawlaChoon Kit TangEng Eong OoiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bo Sun Karin B. Sundström Jun Jie Chew Pradeep Bist Esther S. Gan Hwee Cheng Tan Kenneth C. Goh Tanu Chawla Choon Kit Tang Eng Eong Ooi Dengue virus activates cGAS through the release of mitochondrial DNA
description	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.
format	article
author	Bo Sun Karin B. Sundström Jun Jie Chew Pradeep Bist Esther S. Gan Hwee Cheng Tan Kenneth C. Goh Tanu Chawla Choon Kit Tang Eng Eong Ooi
author_facet	Bo Sun Karin B. Sundström Jun Jie Chew Pradeep Bist Esther S. Gan Hwee Cheng Tan Kenneth C. Goh Tanu Chawla Choon Kit Tang Eng Eong Ooi
author_sort	Bo Sun
title	Dengue virus activates cGAS through the release of mitochondrial DNA
title_short	Dengue virus activates cGAS through the release of mitochondrial DNA
title_full	Dengue virus activates cGAS through the release of mitochondrial DNA
title_fullStr	Dengue virus activates cGAS through the release of mitochondrial DNA
title_full_unstemmed	Dengue virus activates cGAS through the release of mitochondrial DNA
title_sort	dengue virus activates cgas through the release of mitochondrial dna
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b41daa6c581143b7a27dd423f55e72bf
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Dengue virus activates cGAS through the release of mitochondrial DNA

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