Conventional protein kinase C inhibition prevents alpha interferon-mediated hepatitis C virus replicon clearance by impairing STAT activation

被引:18
作者
Fimia, GM
Evangelisti, C
Alonzi, T
Romani, M
Fratini, F
Paonessa, G
Ippolito, G
Tripodi, M
Piacentini, M
机构
[1] Univ Roma La Sapienza, Natl Inst Infect Dis L Spallanzani, Gene Express Lab, IRCCS, I-00149 Rome, Italy
[2] Univ Roma La Sapienza, Inst Pasteur, Dipartimento Biotecnol Cellulari & Ematol, Sez Genet Mol,Fdn Cenci, I-00149 Rome, Italy
[3] Univ Roma Tor Vergata, Dept Biol, Rome, Italy
[4] Ist Ric Biol Mol P Angletti, Pomezia, Italy
关键词
D O I
10.1128/JVI.78.23.12809-12816.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-alpha), is effective in a limited percentage of patients. The mechanisms by which IFN-alpha interferes with the HCV life cycle and the reasons for limited effectiveness of IFN-alpha 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-alpha-mediated HCV clearance. We reported that conventional protein kinase C (cPKC) activity is important for the effectiveness of IFN-alpha treatment. In cells treated with a cPKC-specific inhibitor, IFN-alpha failed to induce an efficient HCV RNA degradation. The lack of cPKC activity leads to a broad reduction of IFN-alpha-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-alpha-mediated antiviral therapies.
引用
收藏
页码:12809 / 12816
页数:8
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