Dengue virus infection down-regulates differentiation markers in neuroblastoma cells

Abstract

Introduction: Approximately 5% of patients suffering from dengue hemorrhagic fever may have neurological manifestations. However, little information is available about direct infection of neurones by dengue virus.

Objective: To determine the role of neuronal phenotype during DENV infection in human neuroblastoma cell line SH-SY5Y, either induced or not to differentiate by treatment with retinoic acid (RA).

Materials and methods: Neuroblastoma cell line SH-SY5Y was induced to differentiate with RA and infected with DENV. The expression of viral antigen and of two differentiation markers of neurones, GAP-43 and synaptophysin, was evaluated quantitatively. Postinfection viability was also evaluated by the MTT technique.

Results: It was found that differentiated cells are more susceptible to infection by dengue virus since more viral antigen was found in them than in the undifferentiated ones. DENV infection caused death in both cell types, but the rate was higher in the undifferentiated ones (40.3% vs 21.5%). In addition, DENV infection in differentiated SH-SY5Y cells induced a significant decrease in GAP-43 and synaptophysin expression.

Conclusions: These results allow us to suggest a relationship between DENV infection and neuronal function, which could be important to elucidate the pathogenesis of neurological manifestations occurring in severe dengue disease.