title: Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death.
abstract: 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-kappaB 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-kappaB 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.
authors.affiliation: Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Marianneau
authors.forename: A
authors.initials: A
authors.lastname: Cardona
authors.forename: L
authors.initials: L
authors.lastname: Edelman
authors.forename: V
authors.initials: V
authors.lastname: Deubel
authors.forename: P
authors.initials: P
authors.lastname: Desprès
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D053938:DNA Fragmentation; D003716:Dengue Virus / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014779:Virus Replication
chemical_list: D016328:NF-kappa B