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 DENV-induced 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.

Original languageEnglish
Article number7023
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Dengue Virus
Virus Diseases
Clathrin
Vacuolar Proton-Translocating ATPases
Endocytosis
Viral Encephalitis
Virus Release
In Vitro Techniques
Double-Stranded RNA
Viral Proteins
Virus Replication
Hippocampus
Cell Line
Mortality

ASJC Scopus subject areas

  • General

Cite this

Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways. / Ho, Min Ru; Tsai, Tsung Ting; Chen, Chia Ling; Jhan, Ming Kai; Tsai, Cheng Chieh; Lee, Yi Chao; Chen, Chun Han; Lin, Chiou Feng.

In: Scientific Reports, Vol. 7, No. 1, 7023, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Jhan, Ming Kai

AU - Tsai, Cheng Chieh

AU - Lee, Yi Chao

AU - Chen, Chun Han

AU - Lin, Chiou Feng

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