Sendai virus (SeV) encodes two accessory proteins, V and C, in the alternative reading frames in the P gene that are accessed transcriptionally (V) or translationally (C). The C protein is expressed as a nested set of four C-coterminal proteins, C, C, Y1, and Y2, that use different initiation codons. Using HeLa cell lines constitutively expressing the various C proteins, we previously found that the smallest (the 175-residue Y2) of the four C proteins was fully capable of counteracting the antiviral action of interferons (IFNs) and inhibiting viral RNA synthesis and that the C-terminal half of 106 residues was sufficient for both of these inhibitory functions Sendai virus (SeV) is an enveloped virus with a linear, nonsegmented, negative-sense RNA genome of 15,384 nucleotides and belongs to the genus Respirovirus of the subfamily Paramyxovirinae. SeV contains six genes in the order 3Ј-(leader)-N-P-M-F-HN-L-(trailer)-5Ј on the genome. The monocistronic mRNAs are transcribed by the viral RNA polymerase composed of L and P proteins (16). However, the P gene is exceptional in that it gives rise to multiple protein species by a process known as RNA editing and by the use of an overlapping open reading frame (ORF). The P protein is translated from the unedited mRNA, which is the exact copy of the P gene, while the V protein is translated from the edited mRNA, in which one nontemplated G residue is cotranscriptionally inserted to the editing position. The P and V proteins, therefore, have a common N terminus but have different C termini because the reading frame for V changes by ϩ1 relative to the P frame (for a review, see references 33 and 38). The V protein is encoded by almost all viruses that are members of the subfamily Paramyxovirinae. The unique C-terminal region of V contains seven cysteine residues highly conserved among paramyxoviruses, forms zinc finger-like motifs, and, indeed, binds Zn 2ϩ (7,20,35,44,51). The C protein is translated from the Ϫ1 reading frame relative to the frame common to P and V. The SeV P and V proteins are initiated at the AUG codon at position 104, whereas the SeV C reading frame produces a nested set of CЈ, C, Y1, and Y2 proteins initiating, respectively, at a non-AUG (ACG) codon at position 81 and at AUG codons at positions 114, 183, and 201 (4, 15, 45). The CЈ, C, Y1, and Y2 proteins are terminated at the same position 726 and are collectively called C proteins. Among them, the C protein is the major species expressed in infected cells, at a molar ratio severalfold higher than that of the other three proteins (32). The C proteins are expressed by the viruses belonging to three genera, Respirovirus, Morbillivirus, and Henipahvirus, and by Tupaia paramyxovirus-like viruses, but they are not expressed by the viruses belonging to two genera, Rubulavirus and Avulavirus of Paramyxovirinae (reviewed in reference 37). The amino acid sequence of the C proteins is well conserved within each genus