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J. Virol., Apr 1997, 3244-3249, Vol 71, No. 4
Copyright © 1997, American Society for Microbiology

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

P Marianneau, A Cardona, L Edelman, V Deubel and P Despres
Unite des Arbovirus et Virus des Fievres Hemorragiques, Institut Pasteur, Paris, France.

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.


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