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)-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.

Highlights

  • Infections caused by all four dengue virus (DENV) serotypes cause dengue fever and severe dengue, arthropod-borne viral diseases that are endemically reported in the Eastern Mediterranean, American, South-East Asian, Western Pacific and African regions [1]

  • Our previous studies showed that DENV infection increases microglial cell migration through the TLR3-regulated pathway [17]

  • To investigate the roles of common chemotactic factors generally involved in cell migration, microglial conditioned medium (MCM) was collected at 12 h post-infection and tested for its effect on cell motility

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Summary

Introduction

Infections caused by all four dengue virus (DENV) serotypes cause dengue fever and severe dengue, arthropod-borne viral diseases that are endemically reported in the Eastern Mediterranean, American, South-East Asian, Western Pacific and African regions [1]. Dengue fever is predominantly characterized in dengue patients by clinical signs that include the presence of a fever, rash, and headache. DENV infection may induce severe dengue in patients, as revealed by the presence of many indicators, including plasma leakage, bleeding, loss of consciousness, severe gastrointestinal and organ impairment, and other unusual manifestations [1,2]. In these patients with severe dengue, the prospective lethality should be determined. Antiviral drugs and preventive vaccines are currently being tested in several clinical trials and experimental animal models [5,6]

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