ReferenceID 389
Hepatitis C virus non-structural 5B protein interacts with cyclin A2 and regulates viral propagation
J Hepatol
BACKGROUND & AIMS: Hepatitis C virus (HCV) requires host cellular proteins for its own propagation. To identify the cellular factors necessary for HCV propagation, we have recently screened the small interfering RNA (siR
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Record Fields
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- Reference Id
- 389
- Evidence Id
- 16979
- Core Evidence Id
- 16979
- Source Reference Id
- 754
- Herb2 Reference Id
- HBREF001296
- Subject Paper Key
- HBIN047423_22796893
- Pubmed Id
- 22796893
- Doi
- 10.1016/j.jhep.2012.07.006
- Paper Title
- Hepatitis C virus non-structural 5B protein interacts with cyclin A2 and regulates viral propagation
- Paper Abstract
- BACKGROUND & AIMS: Hepatitis C virus (HCV) requires host cellular proteins for its own propagation. To identify the cellular factors necessary for HCV propagation, we have recently screened the small interfering RNA (siRNA) library targeting cell cycle genes using cell culture grown HCV (HCVcc)-infected cells. In the current study, we have selected and characterized the gene encoding Cyclin A2 (CycA2). Deregulation of CycA2 has been implicated in many types of cancers, including hepatocellular carcinoma. METHODS: The effects of CycA2 on HCV propagation were investigated by siRNA-mediated knockdown assay, in vitro and in vivo protein binding assays, luciferase reporter gene assay, and immunoblot assay. RESULTS: We showed that siRNA-mediated depletion of CycA2 significantly inhibited HCV replication in both HCV subgenomic replicon cells and HCVcc-infected cells. Furthermore, HCV non-structural 5B (NS5B) specifically interacted with CycA2 in vitro and in vivo. Protein interaction was mediated through the cyclin box of CycA2 and the palm domain of NS5B. We further showed that R/HxL motif in the palm domain of HCV NS5B mediated protein interaction with CycA2 and this interaction was necessary for HCV replication. Moreover, we demonstrated that tylophorine, the natural plant product exerting a CycA2 inhibitory function, abrogated HCV replication. CONCLUSIONS: HCV regulates CycA2 via NS5B protein for its own propagation. In addition, tylophorine may be a potential therapeutic agent for HCV.
- Journal
- J Hepatol
- Publish Year
- 2012
- Experiment Subject
- hcv (hcvcc)-infected cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Hepatitis C Virus
- Paper Title Cn
- Paper Title En
- Hepatitis C virus non-structural 5B protein interacts with cyclin A2 and regulates viral propagation
- Bilingual Status
- semi_complete