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Updated: Jun 25, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
IDO mutants cross resistant to type I interferon retain p91-dependent gene induction
Genetic analysis revealed p91 is crucial for interferon signaling. However, specific mutants suggest indoleamine 2,3-dioxygenase (IDO) induction involves distinct proteins, not directly linked to p91 activation.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- p91 is essential for type I and type II interferon signaling.
- Mutants resistant to interferon-gamma showed a signaling defect affecting indoleamine 2,3-dioxygenase (IDO) induction.
- IDO induction was not observed with type I interferon, despite a relevant upstream sequence.
Purpose of the Study:
- To investigate the effects of type I and type II interferons on interferon-stimulated gene mRNA accumulation in ME180 mutants.
- To identify alterations in cellular proteins resulting from the mutation.
- To determine if p91 activation is directly correlated with IDO induction.
Main Methods:
- Analysis of ME180 mutants resistant to interferon-gamma.
- Examination of interferon-stimulated gene mRNA accumulation (6-16, IRF1, p68).
- Assessment of p91 phosphorylation and analysis of cellular protein alterations using two-dimensional gel electrophoresis.
Main Results:
- p91 phosphorylation was normal in mutants.
- Induction of the p91-responsive gene 6-16 was unaffected.
- IRF1 and p68 mRNA accumulation kinetics differed, and 20 peptides showed altered biochemistry in mutants.
Conclusions:
- IDO induction is regulated by a separate protein set, independent of p91 activation.
- The signaling pathway for IDO induction differs from the canonical p91-mediated interferon response.
- Mutations impact cellular protein biochemistry, affecting interferon-stimulated gene expression kinetics.
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