Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease

Eileen Foy, Kui Li, Chunfu Wang, Rhea Sumpter, Masanori Ikeda, Stanley M. Lemon, Michael Gale

Research output: Contribution to journalArticle

649 Citations (Scopus)

Abstract

Persistent infections with hepatitis C virus (HCV) are likely to depend on viral inhibition of host defenses. We show that the HCV NS3/4A serine protease blocks the phosphorylation and effector action of interferon regulatory factor-3 (IRF-3), a key cellular antiviral signaling molecule. Disruption of NS3/4A protease function by mutation or a ketoamide peptidomimetic inhibitor relieved this blockade and restored IRF-3 phosphorylation after cellular challenge with an unrelated virus. Furthermore, dominant-negative or constitutively active IRF-3 mutants, respectively, enhanced or suppressed HCV RNA replication in hepatoma cells. Thus, the NS3/4A protease represents a dual therapeutic target, the inhibition of which may both block viral replication and restore IRF-3 control of HCV infection.

Original languageEnglish (US)
Pages (from-to)1145-1148
Number of pages4
JournalScience
Volume300
Issue number5622
DOIs
StatePublished - May 16 2003

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Interferon Regulatory Factor-3
Serine Proteases
Hepacivirus
Peptide Hydrolases
Phosphorylation
Peptidomimetics
Virus Diseases
Virus Replication
Antiviral Agents
Hepatocellular Carcinoma
RNA
Viruses
Mutation
Infection

All Science Journal Classification (ASJC) codes

  • General

Cite this

Foy, E., Li, K., Wang, C., Sumpter, R., Ikeda, M., Lemon, S. M., & Gale, M. (2003). Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science, 300(5622), 1145-1148. https://doi.org/10.1126/science.1082604

Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. / Foy, Eileen; Li, Kui; Wang, Chunfu; Sumpter, Rhea; Ikeda, Masanori; Lemon, Stanley M.; Gale, Michael.

In: Science, Vol. 300, No. 5622, 16.05.2003, p. 1145-1148.

Research output: Contribution to journalArticle

Foy, E, Li, K, Wang, C, Sumpter, R, Ikeda, M, Lemon, SM & Gale, M 2003, 'Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease', Science, vol. 300, no. 5622, pp. 1145-1148. https://doi.org/10.1126/science.1082604
Foy, Eileen ; Li, Kui ; Wang, Chunfu ; Sumpter, Rhea ; Ikeda, Masanori ; Lemon, Stanley M. ; Gale, Michael. / Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. In: Science. 2003 ; Vol. 300, No. 5622. pp. 1145-1148.
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