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Updated: Jul 19, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Translational inhibition and increased interferon induction in cells infected with C protein-deficient measles virus
Yuichiro Nakatsu1, Makoto Takeda, Shinji Ohno
1Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Abstract:
In addition to the phosphoprotein, the P gene of measles virus (MV) also encodes the V and C proteins by an RNA editing process and by alternative initiation of translation in a different reading frame, respectively. Although the MV C protein is required for efficient MV replication in vivo and in some cultured cells, its exact functions in virus infection are currently unclear. Here, we report that a recombinant MV lacking the C protein (MVDeltaC) grew poorly in a human cell line possessing the intact interferon (IFN) pathway and that this growth defect was associated with reduced viral translation and genome replication. The translational inhibition was correlated with phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Moreover, increased IFN induction was observed in MVDeltaC-infected cells. The NS1 protein of influenza virus, which binds to double-stranded RNA (dsRNA) and consequently inhibits IFN induction and dsRNA-dependent protein kinase activation, complemented the growth defect of MVDeltaC. These results indicate that the MV C protein inhibits IFN induction and modulates host antiviral responses, thereby ensuring MV growth in host cells.
Insights
The measles virus C protein is crucial for viral growth by suppressing the host
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- The measles virus (MV) P gene encodes multiple proteins, including the C protein, through RNA editing and alternative translation initiation.
- The precise role of the MV C protein in viral infection and host interactions remains largely undetermined.
Purpose of the Study:
- To elucidate the function of the measles virus C protein in viral replication and host immune response modulation.
- To investigate the impact of C protein deficiency on viral translation, genome replication, and interferon induction.
Main Methods:
- Generation of a recombinant MV lacking the C protein (MVΔC).
- Assessment of MVΔC growth, viral translation, and genome replication in human cell lines with intact interferon pathways.
- Analysis of host antiviral responses, including interferon induction and protein kinase activation.
- Complementation studies using the NS1 protein of influenza virus.
Main Results:
- MVΔC exhibited poor growth in human cells, linked to reduced viral translation and genome replication.
- Translational inhibition in MVΔC-infected cells correlated with phosphorylation of eukaryotic translation initiation factor 2 alpha.
- Cells infected with MVΔC showed increased interferon induction.
- The influenza virus NS1 protein could complement the growth defect of MVΔC, indicating a role in inhibiting interferon.
Conclusions:
- The measles virus C protein plays a critical role in inhibiting host interferon induction.
- By modulating host antiviral responses, the MV C protein facilitates efficient viral replication and propagation.
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