FCCC LOGO Faculty Publications
Guo JT , Zhu Q , Seeger C
Cytopathic and noncytopathic interferon responses in cells expressing hepatitis C virus subgenomic replicons
Journal of Virology. 2003 Oct;77(20) :10769-10779
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Hepatitis C virus (HCV) is the only known positive-stranded RNA virus that causes persistent lifelong infections in humans. Accumulation of HCV RNA can be inhibited with alpha interferon (IFN-alpha) in vivo and in culture cells. We used cell-based assay systems to investigate the mechanisms responsible for the cytokine-induced inhibition of HCV replication. The results showed that IFN-a could suppress the accumulation of viral RNA by a noncytopathic pathway and could also induce apoptosis of virally infected cells in a concentration and cell line-dependent fashion. Whereas the noncytopathic IFN-a response depended on a functional Jak-STAT signal transduction pathway, it did not appear to require double-stranded RNA-dependent pathways. Moreover, we found that functional proteasomes were required for establishment of the IFN-a response against HCV. Based on the results described in this study we propose a model for the mechanism by which IFN-a therapy suppresses HCV replicatio! n in chronic infections by both cytopathic and noncytopathic means.
English Article 0022-538X