Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways

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...

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Autores principales:	Min-Ru Ho, Tsung-Ting Tsai, Chia-Ling Chen, Ming-Kai Jhan, Cheng-Chieh Tsai, Yi-Chao Lee, Chun-Han Chen, Chiou-Feng Lin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9000d0df5a274de08cebf48ccb2294cd
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spelling	oai:doaj.org-article:9000d0df5a274de08cebf48ccb2294cd2021-12-02T15:05:08ZBlockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways10.1038/s41598-017-07023-z2045-2322https://doaj.org/article/9000d0df5a274de08cebf48ccb2294cd2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07023-zhttps://doaj.org/toc/2045-2322Abstract 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.Min-Ru HoTsung-Ting TsaiChia-Ling ChenMing-Kai JhanCheng-Chieh TsaiYi-Chao LeeChun-Han ChenChiou-Feng LinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min-Ru Ho Tsung-Ting Tsai Chia-Ling Chen Ming-Kai Jhan Cheng-Chieh Tsai Yi-Chao Lee Chun-Han Chen Chiou-Feng Lin Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
description	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.
format	article
author	Min-Ru Ho Tsung-Ting Tsai Chia-Ling Chen Ming-Kai Jhan Cheng-Chieh Tsai Yi-Chao Lee Chun-Han Chen Chiou-Feng Lin
author_facet	Min-Ru Ho Tsung-Ting Tsai Chia-Ling Chen Ming-Kai Jhan Cheng-Chieh Tsai Yi-Chao Lee Chun-Han Chen Chiou-Feng Lin
author_sort	Min-Ru Ho
title	Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
title_short	Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
title_full	Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
title_fullStr	Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
title_full_unstemmed	Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
title_sort	blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9000d0df5a274de08cebf48ccb2294cd
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Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways

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