Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I

Rhea Sumpter, Yueh Ming Loo, Eileen Foy, Kui Li, Mitsutoshi Yoneyama, Takashi Fujita, Stanley M. Lemon, Michael Gale

Research output: Contribution to journalArticle

601 Citations (Scopus)

Abstract

Virus-responsive signaling pathways that induce alpha/beta interferon production and engage intracellular immune defenses influence the outcome of many viral infections. The processes that trigger these defenses and their effect upon host permissiveness for specific viral pathogens are not well understood. We show that structured hepatitis C virus (HCV) genomic RNA activates interferon regulatory factor 3 (IRF3), thereby inducing interferon in cultured cells. This response is absent in cells selected for permissiveness for HCV RNA replication. Studies including genetic complementation revealed that permissiveness is due to mutational inactivation of RIG-I, an interferon-inducible cellular DExD/H box RNA helicase. Its helicase domain binds HCV RNA and transduces the activation signal for IRF3 by its caspase recruiting domain homolog. RIG-I is thus a pathogen receptor that regulates cellular permissiveness to HCV replication and, as an interferon-responsive gene, may play a key role in interferon-based therapies for the treatment of HCV infection.

Original languageEnglish (US)
Pages (from-to)2689-2699
Number of pages11
JournalJournal of Virology
Volume79
Issue number5
DOIs
StatePublished - Mar 1 2005

Fingerprint

Permissiveness
RNA helicases
RNA Helicases
Hepatitis C virus
Virus Replication
Hepacivirus
Antiviral Agents
interferons
Interferons
RNA
Interferon Regulatory Factor-3
Virus Diseases
genetic complementation
interferon-beta
pathogens
Interferon-beta
caspases
Caspases
virus replication
Interferon-alpha

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. / Sumpter, Rhea; Loo, Yueh Ming; Foy, Eileen; Li, Kui; Yoneyama, Mitsutoshi; Fujita, Takashi; Lemon, Stanley M.; Gale, Michael.

In: Journal of Virology, Vol. 79, No. 5, 01.03.2005, p. 2689-2699.

Research output: Contribution to journalArticle

Sumpter, Rhea ; Loo, Yueh Ming ; Foy, Eileen ; Li, Kui ; Yoneyama, Mitsutoshi ; Fujita, Takashi ; Lemon, Stanley M. ; Gale, Michael. / Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. In: Journal of Virology. 2005 ; Vol. 79, No. 5. pp. 2689-2699.
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