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

• Published in: Viruses Vol. 10; no. 12; p. 690
• Main Authors: Jhan, Ming-Kai, Shen, Ting-Jing, Tseng, Po-Chun, Wang, Yung-Ting, Lin, Chiou-Feng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.12.2018; MDPI
• Subjects: Animals; Antibodies; Brain; c-Jun protein; Caveolae; Caveolae - drug effects; Cell activation; Cell adhesion & migration; Cell Line; Cell Movement; Chemokine CCL19 - immunology; Chemokines; Chemotactic factors; Culture Media, Conditioned; Cytokines; Cytotoxicity; Dengue fever; dengue virus; Dengue Virus - immunology; Encephalitis; Infections; Inflammation; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK protein; Kinases; Leukocyte migration; Ligands; Lipid rafts; Lipids; Macrophage inflammatory protein; Membrane Microdomains - drug effects; Mice; Microglia; Microglia - cytology; Microglia - virology; Microglial cells; migration; MIP-3β; Motility; Neurotoxicity; Nystatin - pharmacology; Pathogenesis; Signal Transduction; Statistical analysis; TLR3 protein; Toll-like receptors; Transcription factors; Ultraviolet Rays; Wound healing; United States > US; migration; microglia; MIP-3β; caveolae; dengue virus
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v10120690

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)-3β 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-3β and its effect on the JNK signaling pathways mediates DENV-induced BV2 microglial cell migration.