Speaker:
Associate Professor Henry Mok Yu-Keung

Synopsis:
Dengue virus (DENV) is mosquito-borne virus that survive by cycling between mosquito vectors, principally Aedes aegypti, and human hosts. To archive successful transmission, the DENV in the blood meal from an infected person needs to pass through the midgut barrier of the mosquito. This allows the DENV to infect the salivary gland of the mosquito and then pass onto the next human host through biting and blood sucking. Our previous work on the structural study of protein factors in mosquito that could affect DENV transmission identified a Kazal-type protease inhibitor called Aedes trypsin inhibitor (AaTI), which turns out to be a specific inhibitor of human plasmin. We have determined the crystal structure of AaTI in complex with μ-plasmin. Using bio-layer interferometry (BLI), we show that DENV, plasmin, and AaTI physically interact to form a tripartite complex. We found that both kringle-4 and -5 domains of plasmin are required for interaction with DENV. Site-directed mutagenesis and amide-proton exchange spectrometry are being used to identify the exact residues involved in interaction between plasmin kringle domains and E-protein of DENV.

For enquiries, please contact:

Mr Ambert Ang
Phone: +65  65162711
Email: DBS_outreach@nus.edu.sg