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.
| Original language | English |
|---|---|
| Pages (from-to) | 12809-12816 |
| Number of pages | 8 |
| Journal | Journal of Virology |
| Volume | 78 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Dec 2004 |
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ASJC Scopus subject areas
- Immunology
Cite this
Conventional protein kinase C inhibition prevents alpha interferon-mediated hepatitis C virus replicon clearance by impairing STAT activation. / Fimia, Gian Maria; Evangelisti, Cristina; Alonzi, Tonino; Romani, Marta; Fratini, Federica; Paonessa, Giacomo; Ippolito, Giuseppe; Tripodi, Marco; Piacentini, Mauro.
In: Journal of Virology, Vol. 78, No. 23, 12.2004, p. 12809-12816.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Conventional protein kinase C inhibition prevents alpha interferon-mediated hepatitis C virus replicon clearance by impairing STAT activation
AU - Fimia, Gian Maria
AU - Evangelisti, Cristina
AU - Alonzi, Tonino
AU - Romani, Marta
AU - Fratini, Federica
AU - Paonessa, Giacomo
AU - Ippolito, Giuseppe
AU - Tripodi, Marco
AU - Piacentini, Mauro
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=8644287462&partnerID=8YFLogxK
U2 - 10.1128/JVI.78.23.12809-12816.2004
DO - 10.1128/JVI.78.23.12809-12816.2004
M3 - Article
C2 - 15542633
AN - SCOPUS:8644287462
VL - 78
SP - 12809
EP - 12816
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 23
ER -