Dengue virus induces apoptosis in SH-SY5Y human neuroblastoma cells

Abstract

Introduction: Dengue is a human disease caused by a virus with the same name, which is transmitted by the bite of Aedes mosquitoes. The infection has a wide range of clinical presentations ranging from asymptomatic to fatal cases, with the pediatric population being the most susceptible. According to the new classification of the disease, the neurological manifestations are considered a criterion for the diagnosis of severe dengue. Objective: To evaluate the possible mechanisms involved in the onset of neurological signs in a cell line of human neurons as a model of infection with dengue virus type 2 (DENV-2). Materials and methods: Susceptibility and permissiveness of the SH-SY5Y line to infection by DENV-2 was analyzed, showing that the proportions of viral infection and production are similar to those of primate cells used as positive control for infection. Results: Infection induced a cytopathic effect on the neuroblastoma line characterized by apoptotic cell death process, increasing the proportion of annexin V and TUNEL positive cells and an upregulation of TNF-α. Treatment with anti-TNF-α antibody increased slightly cell survival of infected cells. The addition of exogenous TNF-α to the infected cultures enhanced cell death. Conclusion: These results as a whole suggest that the upregulation of TNF-α could be part of the process that induces cell damage and death in cases of dengue encephalitis.