Isolation and gene analysis of interferon α-resistant cell clones of the hepatitis C virus subgenome
| Autor: | Naoki Ogura, Tohru Noguchi, Tomoko Otsubaki, Satoru Ikeda, Kunitada Shimotohno, Izuru Ando |
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| Rok vydání: | 2008 |
| Předmět: |
Interferon resistance
Genes Viral viruses Hepatitis C virus Hepacivirus Viral Nonstructural Proteins Biology Transfection medicine.disease_cause Nonstructural protein NS5A Transactivation Cell Line Tumor Virology Drug Resistance Viral medicine Humans Replicon Phosphorylation NS5A Gene NS3 Stat-1 Interferon-alpha virus diseases RNA biochemical phenomena metabolism and nutrition Molecular biology digestive system diseases Clone Cells STAT1 Transcription Factor Mutation RNA Viral |
| Zdroj: | Virology. 375:424-432 |
| ISSN: | 0042-6822 |
| Popis: | Hepatitis C virus (HCV) proteins appear to play an important role in IFN-resistance, but the molecular mechanism remains unclear. To clarify the mechanism in HCV replicon RNA harboring Huh-7 cells (Huh-9-13), we isolated cellular clones with impaired IFNalpha-sensitivity. Huh-9-13 was cultured for approximately 2 months in the presence of IFNalpha, and 4 IFNalpha-resistant cell clones showing significant resistances were obtained. When total RNA from clones was introduced into Huh-7 cells, the transfected cells also exhibited IFNalpha-resistance. Although no common mutations were present, mutations in NS3 and NS5A regions were accumulated. Transactivation of IFNalpha and IFNalpha-stimulated Stat-1 phosphorylation were reduced, and the elimination of HCV replicon RNA from the clones restored the IFNalpha signaling. These results suggest that the mutations in the HCV replicon RNA, at least in part, cause an inhibition of IFN signaling and are important for acquisition of IFNalpha resistance in Huh-9-13. |
| Databáze: | OpenAIRE |
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