Cytopathic and Noncytopathic Interferon Responses in Cells Expressing Hepatitis C Virus Subgenomic Replicons
AUTOR(ES)
Guo, Ju-Tao
FONTE
American Society for Microbiology
RESUMO
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-α) 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-α 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-α 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-α response against HCV. Based on the results described in this study we propose a model for the mechanism by which IFN-α therapy suppresses HCV replication in chronic infections by both cytopathic and noncytopathic means.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=224980Documentos Relacionados
- Identification of the Hepatitis C Virus RNA Replication Complex in Huh-7 Cells Harboring Subgenomic Replicons
- Antiviral Effect and Virus-Host Interactions in Response to Alpha Interferon, Gamma Interferon, Poly(I)-Poly(C), Tumor Necrosis Factor Alpha, and Ribavirin in Hepatitis C Virus Subgenomic Replicons
- Replication Studies Using Genotype 1a Subgenomic Hepatitis C Virus Replicons
- Hepatitis C Virus Subgenomic Replicons in the Human Embryonic Kidney 293 Cell Line
- Hepatitis C Virus Subgenomic Replicons Induce Endoplasmic Reticulum Stress Activating an Intracellular Signaling Pathway