Sebastian AGUIRRE, PhD
Assistant Professor, Department of Microbiology,
Icahn School of Medicine at Mount Sinai, New York, NY, USA
“Collateral damage during dengue virus infection: Making sense of DNA by cGAS”
Mardi 10 Avril 2018 à 12h00
Auditorium Centre François Jacob
For the last decades Dengue virus (DENV) has dramatically increased its global incidence, being now endemic in more than 100 countries. In order to stablish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Some studies have deciphered mechanisms that rely on viral proteins to strategically target crucial components of the type I IFN system. Here we report that the DNA sensor cGAS is involved in early detection of DENV infection, by recognizing misplaced host DNA. By using biochemical and immunofluorescence techniques, we demonstrate a novel mechanism by which cGAS sense cellular damage upon DENV infection. Furthermore, the NS2B protease co-factor specifically interacts with cGAS during infection and promotes its degradation in a lysosome dependent mechanism. This degradation results in an inhibition of the cGAS/STING cytosolic DNA sensing pathway in primary human dendritic cells.