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

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

Nature microbiology (2017-03-28)
Sebastian Aguirre, Priya Luthra, Maria T Sanchez-Aparicio, Ana M Maestre, Jenish Patel, Francise Lamothe, Anthony C Fredericks, Shashank Tripathi, Tongtong Zhu, Jessica Pintado-Silva, Laurence G Webb, Dabeiba Bernal-Rubio, Alexander Solovyov, Benjamin Greenbaum, Viviana Simon, Christopher F Basler, Lubbertus C F Mulder, Adolfo García-Sastre, Ana Fernandez-Sesma
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.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Anti-DNA Antibody, clone AC-30-10, clone AC-30-10, Chemicon®, from mouse