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Sendai virus defective-interfering genomes and the activation of interferon-beta
Laura Strahle1, Dominique Garcin, Daniel Kolakofsky
1Department of Microbiology and Molecular Medicine, University of Geneva School of Medicine, 11 Ave de Champel, CH1211 Geneva, Switzerland.
Virology
|April 25, 2006
Summary
Sendai virus (SeV) stocks with defective-interfering (DI) genomes, particularly copyback DI genomes, strongly activate interferon beta (IFNbeta). This activation correlates with dsRNA formation and is enhanced when viral proteins that block antiviral responses are less expressed.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Sendai virus (SeV) stocks containing defective-interfering (DI) genomes are known to activate interferon beta (IFNbeta).
- The precise mechanism and specific DI genome types responsible for potent IFNbeta activation remained unclear.
Purpose of the Study:
- To compare the ability of different Sendai virus (SeV) defective-interfering (DI) genomes to activate the IFNbeta promoter.
- To elucidate the role of DI genome characteristics and viral proteins in IFNbeta activation.
Main Methods:
- Comparison of SeV stocks with various DI genomes (copyback, internal deletion, nondefective) for IFNbeta promoter activation using reporter genes.
- Analysis of the correlation between IFNbeta activation, DI genome replication, dsRNA formation, and viral protein expression (V and C proteins).
- Assessment of poly-I:C-induced activation as a control.
Main Results:
- Copyback DI genomes were primarily responsible for strong IFNbeta activation.
- IFNbeta activation correlated with the ability of copyback DI genomes to self-anneal and form double-stranded RNA (dsRNA).
- Activation levels were proportional to DI genome replication and the ratio of DI to nondefective (ND) genomes.
- Over-expression of viral V and C proteins inhibited copyback DI-induced IFNbeta activation, similar to poly-I:C-induced activation, indicating a dsRNA-dependent mechanism.
Conclusions:
- Copyback DI genomes in SeV stocks are the main drivers of potent IFNbeta activation.
- This activation occurs via dsRNA intermediates and is potentiated by reduced expression of viral IFN-antagonistic proteins.
- SeV stocks rich in copyback DI genomes represent a unique method for robustly stimulating the host antiviral response.
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