Sensitization to Fas-mediated apoptosis by dengue virus capsid protein

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are important public health problems in tropical regions. Abnormal hemostasis and plasma leakage are the main patho-physiological changes in DHF. However, hepatomegaly, hepatocellular necrosis and fulminant hepatic failure are occasionally observed in patients with DHF. Dengue virus-infected liver cells undergo apoptosis but the underlying molecular mechanism remains unclear. Using a yeast two-hybrid screen, we found that dengue virus capsid protein (DENV C) physically interacts with the human death domain-associated protein Daxx, a Fas-associated protein. The interaction between DENV C and Daxx in dengue virus-infected liver cells was also demonstrated by co-immunoprecipitation and double immunofluorescence staining. The two proteins were predominantly co-localized in the cellular nuclei. Fas-mediated apoptotic activity in liver cells constitutively expressing DENV C was induced by anti-Fas antibody, indicating that the interaction of DENV C and Daxx involves in apoptosis of dengue virus-infected liver cells.