Dengue virus infection increases microglial cell migration

Ming Kai Jhan; Tsung Ting Tsai; Chia Ling Chen; Cheng Chieh Tsai; Yi Lin Cheng; Yi Chao Lee; Chiung Yuan Ko; Yee Shin Lin; Chih Peng Chang; Liang Tzung Lin; Chiou Feng Lin

doi:10.1038/s41598-017-00182-z

Dengue virus infection increases microglial cell migration

Ming Kai Jhan, Tsung Ting Tsai, Chia Ling Chen, Cheng Chieh Tsai, Yi Lin Cheng, Yi Chao Lee, Chiung Yuan Ko, Yee Shin Lin, Chih Peng Chang, Liang Tzung Lin, Chiou Feng Lin

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Abstract

Activated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated DENV caused infection, including viral entry, RNA replication, viral protein expression, and virus release, in the murine microglial cell line BV2. DENV infection caused an increase in the formation of the multipolar phenotype in vitro and in vivo without affecting cell growth and cytotoxicity. DENV infection considerably increased cell motility and disrupting either actin filaments or clathrin retarded such effect. Increase in cell migration was only occurred by DENV infection following a clathrin-regulated endocytosis of DENV entry. Ultravioletinactivated DENV did not affect cell migration, and pharmacologically blocking toll-like receptor (TLR) 3 and TLR3-related signaling pathways reduced the DENV-induced increase in cell migration. These results demonstrate an advanced effect of DENV infection on microglial migration via a mechanism involving viral entry, RNA release, and TLR3 signal activation.

Original language	English
Article number	91
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-00182-z
Publication status	Published - Jan 1 2017

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Jhan, M. K., Tsai, T. T., Chen, C. L., Tsai, C. C., Cheng, Y. L., Lee, Y. C., Ko, C. Y., Lin, Y. S., Chang, C. P., Lin, L. T., & Lin, C. F. (2017). Dengue virus infection increases microglial cell migration. Scientific Reports, 7(1), [91]. https://doi.org/10.1038/s41598-017-00182-z

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abstract = "Activated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated DENV caused infection, including viral entry, RNA replication, viral protein expression, and virus release, in the murine microglial cell line BV2. DENV infection caused an increase in the formation of the multipolar phenotype in vitro and in vivo without affecting cell growth and cytotoxicity. DENV infection considerably increased cell motility and disrupting either actin filaments or clathrin retarded such effect. Increase in cell migration was only occurred by DENV infection following a clathrin-regulated endocytosis of DENV entry. Ultravioletinactivated DENV did not affect cell migration, and pharmacologically blocking toll-like receptor (TLR) 3 and TLR3-related signaling pathways reduced the DENV-induced increase in cell migration. These results demonstrate an advanced effect of DENV infection on microglial migration via a mechanism involving viral entry, RNA release, and TLR3 signal activation.",

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