Type I interferons (IFNalpha/beta) are an important part of innate immunity to viral infections because they induce an antiviral response and limit viral replication until the adaptive response clears the infection. Since the nonstructural proteins of several paramyxoviruses inhibit the IFNalpha/beta response, we chose to explore the role of the C protein of measles virus (MV) in such inhibition. Previous studies have suggested that the MV C protein may serve as a virulence factor, but its role in the pathogenesis of MV remains undefined. In the present study, a recombinant MV strain that does not express the C protein (MV C-) and its parental strain (Ed Tag) were used. Growth of MV C- was restricted in human peripheral blood mononuclear cells and HeLa cells, but in the presence of neutralizing antibodies to IFNalpha/beta, MV C- produced titers that were equivalent to those of Ed Tag. In addition, expression of the MV C protein from plasmid DNA inhibited the production of an IFNalpha/beta responsive reporter gene and, to a lesser extent, inhibited an IFNgamma responsive reporter gene. The ability of the MV C protein to suppress the IFNalpha/beta response was confirmed using a biologic assay. After IFNbeta stimulation, HeLa cells infected with Ed Tag produced five-fold less IFNalpha/beta than cells infected with MV C-. While the mechanism of inhibition remains unclear, these data suggest that the MV C protein plays an important role in the pathogenesis of MV by inhibiting IFNalpha/beta signaling.
The C protein of measles virus inhibits the type I interferon response.
Jessica Shaffer,W. Bellini,P. Rota
Published 2003 in Virology
ABSTRACT
PUBLICATION RECORD
- Publication year
2003
- Venue
Virology
- Publication date
2003-10-25
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- ed tag
The parental measles virus strain used as the comparator for MV C- in the infection experiments.
Aliases: parental strain Ed Tag
- hela cells
A human epithelial cell line used for infection and reporter assays in the study.
- human peripheral blood mononuclear cells
Primary human blood-derived immune cells used as one of the infection targets in the study.
Aliases: PBMCs
- ifnalpha/beta responsive reporter gene
A reporter construct used to measure transcriptional activation downstream of IFN-alpha/beta signaling.
Aliases: IFN-alpha/beta reporter
- ifngamma responsive reporter gene
A reporter construct used to measure transcriptional activation downstream of IFN-gamma signaling.
Aliases: IFN-gamma reporter
- measles virus c protein
A measles virus accessory protein encoded by the C gene and tested here for effects on host interferon signaling.
Aliases: MV C protein, C protein
- mv c-
A recombinant measles virus strain engineered not to express the C protein.
Aliases: C-minus MV, C- virus
- neutralizing antibodies to ifnalpha/beta
Antibodies used in the assays to block IFN-alpha/beta activity and test whether the growth restriction depended on that pathway.
Aliases: anti-IFNalpha/beta antibodies
- type i interferon response
The host IFN-alpha/beta signaling system that induces antiviral responses during infection.
Aliases: IFNalpha/beta response, IFN-alpha/beta response
REFERENCES
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