Dengue virus enters and exits epithelial cells through both apical and basolateral surfaces and perturbs the apical junctional complex

Abstract

Dengue is the most relevant mosquito-borne viral disease in the world. It has been estimated that 390 million infections of dengue occur each year. Dengue virus (DENV) infection can be asymptomatic or can produce a self-limited febrile illness called dengue fever (DF) or a severe form of the infection called severe dengue. In some viruses, the entry and egress from cells, occur in a specific domain of polarized endothelial and epithelial cells. In this study, we investigated whether the entry and release of DENV was polarized in epithelial cells, and evaluated the effect of DENV infection on cellular junctions of epithelial cells. We used MDCK epithelial cells, which serve as an excellent model to study a functional barrier due to the presence of an apical junctional complex (AJC), and showed that entry and release of DENV from the cells, is bipolar. Additionally, we performed paracellular flux, diffusion of membrane lipid, immunofluorescence and immunoblotting assays to evaluate the integrity of the AJC during DENV infection. We observed that at later stages of infection, DENV altered the barrier function causing a decrease in the transepithelial electrical resistance and the degradation and delocalization of TJ and AJ proteins. The present study contributes to understand how DENV traverse epithelia in order to cause a productive infection, and provides insights into the mechanism of DENV pathogenesis.

Keywords: Apical junctional complex; Dengue; Infection; Viral entry.