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Sci Rep. 2017 Jun 15;7(1):3594. doi: 10.1038/s41598-017-03932-1.

Dengue virus activates cGAS through the release of mitochondrial DNA.

Author information

1
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, 169857, Singapore.
2
Duke University School of Medicine, Durham, NC, 27710, USA.
3
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, 169857, Singapore. cktang79@gmail.com.
4
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, 169857, Singapore. engeong.ooi@duke-nus.edu.sg.
5
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. engeong.ooi@duke-nus.edu.sg.
6
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. engeong.ooi@duke-nus.edu.sg.
7
Singapore MIT Alliance in Research and Technology, Infectious Diseases Interdisciplinary Group, Singapore, Singapore. engeong.ooi@duke-nus.edu.sg.

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.

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