Dengue infection of monocytic cells activates ER stress pathways, but apoptosis is induced through both extrinsic and intrinsic pathways

Monocytic cells are believed to be an important mediator of the pathology of dengue disease in cases of secondary infection where pre-existing antibodies from a first infection facilitate virus entry to Fc receptor bearing cells. In this study we assessed the induction of the ER stress in response to infection of monocytic U937 cells with all four DENV serotypes as well as the induction of apoptosis. Clear evidence of ER stress and the production of pro-apoptotic signals were observed, together with activation of caspase 9. Surprisingly, caspase 8 was also activated, independently of caspase 9, and this was accompanied by an increase in the expression of TNF-α, suggesting the simultaneous but independent activation of both extrinsic and intrinsic apoptosis pathways. Both the induction of ER stress and apoptosis were shown to be serotype independent.