C Protein Is Essential for Canine Distemper Virus Virulence and Pathogenicity in Ferrets

The measles (MeV) and canine distemper viruses (CDV) express accessory proteins that regulate the host immune response and enhance replication. The MeV C protein is critical in preventing the generation of excess immunostimulatory double-stranded RNA. C protein-deficient MeV is strongly attenuated compared to wild-type virus, whereas CDV with a similarly disrupted C open reading frame is fully pathogenic. Here we show that CDV can compensate the disrupting mutations by expression of truncated, but apparently functional C proteins from several alternative start codons. We generated a new recombinant CDV that does not express these truncated C protein. This virus was attenuated both in cell culture and in ferrets, and finally resolves the paradox of the MeV and CDV C proteins, showing that both in fact have similar functions important for viral pathogenesis.