The C protein of measles virus inhibits the type I interferon response.
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.
Shaffer
Jessica A
JA
Measles Virus Section, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Bellini
William J
WJ
Rota
Paul A
PA
D004268:DNA-Binding Proteins / Q000502:physiology; D003673:Defective Viruses / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D008459:Measles virus / Q000472:pathogenicity*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D017361:Viral Nonstructural Proteins; D007371:Interferon-gamma