EOH Journal Club Seminar - Spring 2018
Date: Thursday March 29, 2018
Time: 11am - 12pm
Presenter: Meghan Matlack
Paper: Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathway
Authors: Min-Ru Ho, Tsung-Ting Tsai, Chia-Ling Chen, Ming-Kai Jhan, Cheng-Chieh Tsai, Yi-Chao Lee, Chun-Han Chen & Chiou-Feng Li
Abstract: Dengue virus (DENV) infection in neuronal cells was speculated to trigger neuropathy. Herein, we determined the blockade of DENV infection by targeting endocytic pathways in vitro and in vivo. In DENV-infected mouse brains, we previously showed that viral proteins are expressed in neuronal cells around the hippocampus with accompanying neurotoxicity. DENV caused infection, including entry, double-stranded (ds)RNA replication, protein expression, and virus release, followed by cytotoxicity in the mouse neuronal Neuro-2a cell line. Pharmacologically blocking clathrin-mediated endocytosis of the DENV retarded viral replication. Targeting vacuolar-type H+-ATPase (V-ATPase)-based endosomal acidification effectively blocked the DENV replication process, but had no direct effect on viral translation. Blockade of the clathrin- and V-ATPase-based endocytic pathways also attenuated DENVinduced neurotoxicity. Inhibiting endosomal acidification effectively retarded DENV infection, acute viral encephalitis, and mortality. These results demonstrate that clathrin mediated endocytosis of DENV followed by endosomal acidification-dependent viral replication in neuronal cells, which can lead to neurotoxicity.
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