Dengue virus replication in human hepatoma cells activates NF-kappa B which in turn induces apoptotic cell death

The severe outcome of the dengue (DEN) virus infection known as DEN hemorrhagic fever-DEN shock syndrome (DHF-DSS) is, in some cases, accompanied by liver injury, Councilman bodies observed in liver biopsies of DHF-DSS cases may correspond to hepatocytes in apoptosis, We show, here that infection of the hepatoma cell line HepG2 with DEN type 1 virus induced cell death typical of apoptosis late in the virus cycle. The transcription factor NF-kappa B was activated concomitantly with viral protein synthesis and thus before the appearance of apoptotic cells, Inhibition of apoptosis was observed when DEN virus-infected cells were treated with NF-kappa B decoys, indicating the involvement of this transcription factor in induction of cell death, Thus, infected hepatocytes appear to be subject to apoptosis in vitro, and this may be a key element in the pathophysiology of hepatic failure associated with DHF-DSS.