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

Gian Maria Fimia, Cristina Evangelisti, Tonino Alonzi, Marta Romani, Federica Fratini, Giacomo Paonessa, Giuseppe Ippolito, Marco Tripodi, Mauro Piacentini

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 languageEnglish
Pages (from-to)12809-12816
Number of pages8
JournalJournal of Virology
Volume78
Issue number23
DOIs
Publication statusPublished - Dec 2004

Fingerprint

replicon
Replicon
interferon-alpha
Hepatitis C virus
protein kinase C
interferons
Interferon-alpha
Hepacivirus
Protein Kinase C
Interferons
therapeutics
RNA Stability
Virus Diseases
Virus Replication
virus replication
Life Cycle Stages
infection
Antiviral Agents
Tyrosine
tyrosine

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 journalArticle

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AU - Fratini, Federica

AU - Paonessa, Giacomo

AU - Ippolito, Giuseppe

AU - Tripodi, Marco

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