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Nat Microbiol. 2017 Mar 27;2:17037. doi: 10.1038/nmicrobiol.2017.37.

Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection.

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
2
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
3
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
4
Tisch Cancer Institute, Division of Hematology and Medical Oncology, Department of Medicine, Department of Pathology and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
5
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.

Abstract

During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection. Such degradation subsequently results in the inhibition of type I interferon production in the infected cell. Our data demonstrate a mechanism by which cGAS senses cellular damage upon DENV infection.

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PMID:
28346446
DOI:
10.1038/nmicrobiol.2017.37
[Indexed for MEDLINE]

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