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Conventional protein kinase C inhibition prevents alpha interferon-mediated hepatitis C virus replicon clearance by impairing STAT activation
- Source :
- Journal of virology. 78(23)
- Publication Year :
- 2004
-
Abstract
- Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. The only treatment available for HCV infections, alpha interferon (IFN-α), is effective in a limited percentage of patients. The mechanisms by which IFN-α interferes with the HCV life cycle and the reasons for limited effectiveness of IFN-α therapy have not yet been fully elucidated. Using a cell-based HCV replication system and specific kinase inhibitors, we examined the role played by various signaling pathways in the IFN-α-mediated HCV clearance. We reported that conventional protein kinase C (cPKC) activity is important for the effectiveness of IFN-α treatment. In cells treated with a cPKC-specific inhibitor, IFN-α failed to induce an efficient HCV RNA degradation. The lack of cPKC activity leads to a broad reduction of IFN-α-stimulated gene expression due to a significant impairment of STAT1 and STAT3 tyrosine phosphorylation. Thus, modulation of cPKC function by either host or viral factors could influence the positive outcome of IFN-α-mediated antiviral therapies.
- Subjects :
- Gene Expression Regulation, Viral
STAT3 Transcription Factor
Hepatitis C virus
Immunology
Alpha interferon
Hepacivirus
Biology
medicine.disease_cause
Microbiology
Antiviral Agents
Cell Line
chemistry.chemical_compound
Virology
Vaccines and Antiviral Agents
medicine
Humans
STAT1
Protein kinase A
Protein kinase C
Interferon alfa
Protein Kinase C
Interferon-alpha
Tyrosine phosphorylation
DNA-Binding Proteins
STAT1 Transcription Factor
chemistry
Insect Science
biology.protein
Trans-Activators
RNA, Viral
Replicon
Signal transduction
medicine.drug
Subjects
Details
- ISSN :
- 0022538X
- Volume :
- 78
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....a1d7529b677f8e5e423510a97fed5a66