Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.isci.2019.10.056
Title: Increased Mosquito Midgut Infection by Dengue Virus Recruitment of Plasmin Is Blocked by an Endogenous Kazal-type Inhibitor
Authors: Ramesh, Karthik 
Walvekar, Varsha A
Wong, Benjamin 
Sayed, Ahmed Mahmoud Mohammed
Misse, Dorothee
Kini, R Manjunatha 
Mok, Yu Keung 
Pompon, Julien 
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CROSS-REACTIVE ANTIBODIES
PERITROPHIC MATRIX
AEDES-AEGYPTI
COAGULATION
HOST
PATHOGENICITY
FIBRINOLYSIS
PATHOGENESIS
CHILDREN
PROTEIN
Issue Date: 22-Nov-2019
Publisher: CELL PRESS
Citation: Ramesh, Karthik, Walvekar, Varsha A, Wong, Benjamin, Sayed, Ahmed Mahmoud Mohammed, Misse, Dorothee, Kini, R Manjunatha, Mok, Yu Keung, Pompon, Julien (2019-11-22). Increased Mosquito Midgut Infection by Dengue Virus Recruitment of Plasmin Is Blocked by an Endogenous Kazal-type Inhibitor. ISCIENCE 21 : 564--576. ScholarBank@NUS Repository. https://doi.org/10.1016/j.isci.2019.10.056
Abstract: Dengue symptoms include alteration of blood coagulation and fibrinolysis, causing severe hemorrhage and death. Here, we demonstrate that higher concentration of plasmin, the human fibrinolytic factor, in blood meal enhances dengue virus (DENV) infection in mosquito midgut and dissemination in mosquitoes. We also show that mosquitoes express a plasmin-selective Kazal-type inhibitor (AaTI) in the midgut to inhibit plasmin proteolysis and revert the enhanced infection. Using bio-layer interferometry, we show that DENV, plasmin, and AaTI interact to form a tripartite complex. Eventually, plasmin increases midgut internalization of dextran molecules and this is reverted by AaTI. Our study demonstrates that (1) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glycocalyx and enhancing DENV internalization and (2) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.
Source Title: ISCIENCE
URI: https://scholarbank.nus.edu.sg/handle/10635/168870
ISSN: 25890042
DOI: 10.1016/j.isci.2019.10.056
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