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

658 Scopus citations

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

ASJC Scopus subject areas

  • General

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    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