Signaling of Macrophage Inflammatory Protein (MIP)-3ß Facilitates Dengue Virus-Induced Microglial Cell Migration.

ABSTRACT

The infection by dengue virus (DENV) of microglia causes cell activation and migration via a mechanism involving viral entry, RNA release, and Toll-like receptor 3 signaling. In this study, we demonstrated that secreted chemotactic factors present in microglial conditioned medium (MCM) facilitated cell motility in the murine BV2 microglial cells. The pharmacological disruption of lipid rafts/caveolae reduced DENV- and ultraviolet (UV)-inactivated MCM-induced microglial cell migration. An antibody-based cytokine/chemokine array showed an increase in macrophage inflammatory protein (MIP)-3ß in MCM produced using DENV-infected cells. The pharmacological inhibition of c-Jun N-terminal kinase (JNK) retarded UV-MCM-induced microglial cell migration. These results demonstrate that secreted MIP-3ß and its effect on the JNK signaling pathways mediates DENV-induced BV2 microglial cell migration.