Study on Dengue Virus-induced Cell Motility in Microglia

• Main Authors: Ming-Kai Jhan, 詹茗凱
• Other Authors: Chiou-Feng Lin
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/494td7

碩士 === 臺北醫學大學 === 醫學科學研究所 === 104 === Infection of dengue virus (DENV), a positive single-stranded RNA virus in the family of Flavivirus, causes mild and severe dengue diseases. In addition to dengue hemorrhagic fever or dengue shock syndrome, dengue patients partly show neurological manifestations such as acute viral encephalitis. Moreover, animal studies and clinical specimens have demonstrated that activated microglial cells are present in DENV-infected brains; however, the possible effects of DENV on microglia remain unclear. Studies in our laboratory report that DENV infection causes microglial cell infection in vitro and in vivo. This study further investigated the effects of DENV on microglial cells. Here we demonstrated the infectious ability of four serotypes of DENV, including viral entry, RNA replication, viral protein expression, and virus release, in murine microglial cell line BV2. Without affecting cell growth and cytotoxicity, DENV infection caused an increase in the formation of multipolar phenotype. Cell motility was considerably increased following DENV infection. Disrupting either actin filaments or clathrin retarded DENV-increased cell migration while clathrin-regulated endocytosis mediated DENV entry. We further found that Ultraviolet-inactivated DENV did not affect cell migration and pharmacologically blocking toll-like receptor (TLR) 3 can reduced DENV-increased cell migration. Following DENV infection, TLR3-related Src, phosphoinositide 3-kinase, and NF-κB were activated for triggering cell migration. Furthermore, chemokine secretion from DENV-infected microglial cells might be involved in cell migration. These results demonstrate an advanced effect of DENV infection on microglia cell migration through a mechanism involving signaling of viral entry, RNA release, and TLR3 activation.