Rinderpest virus is a morbillivirus and the causative agent of an important disease of cattle and wild bovids. The P genes of all morbilliviruses give rise to two proteins in addition to the P protein itself: use of an alternate start translation site, in a second open reading frame, gives rise to the C protein, while cotranscriptional insertion of an extra base gives rise to the V protein, a fusion of the amino-terminal half of P to a short, highly conserved, cysteine-rich zinc binding domain. Little is known about the function of either of these two proteins in the rinderpest virus life cycle. We have constructed recombinant rinderpest viruses in which the expression of these proteins has been suppressed, individually and together, and studied the replication of these viruses in tissue culture. We show that the absence of the V protein has little effect on the replication rate of the virus but does lead to an increase in synthesis of genome and antigenome RNAs and a change in cytopathic effect to a more syncytium-forming phenotype. Virus that does not express the C protein, on the other hand, is clearly defective in growth in all cell lines tested, and this defect appears to be related to a decreased transcription of mRNA from viral genes. The phenotypes of both individual mutant virus types are both expressed in the double mutant expressing neither V nor C.Rinderpest virus (RPV) belongs to the Morbillivirus genus of the family Paramyxoviridae and is thus related to Measles virus (MV), Canine and Phocid (seal) distemper viruses, the cetacean morbillivirus, and Peste des petits ruminants virus. The disease it causes (rinderpest) has for decades been one of the most widespread and economically important diseases affecting cattle in Africa, the Middle East, and the Indian subcontinent. It has been eliminated from most of these areas in recent years, largely through the efforts of the European Union-and Food and Agriculture Organization-backed EMPRES program, with the aim of global eradication by 2010 (22). Like all of the morbilliviruses, there is only one serotype of RPV, yet wide variation can be found in the pathogenicity of field isolates, from those causing essentially 100% mortality to others in which infection causes barely detectable clinical signs (58, 64). The molecular basis of this variation is unknown.All of the Paramyxoviridae have single-stranded RNA genomes of negative sense, with six viral genes, which are transcribed in order from a single promoter at the 3Ј end of the genome. From the second of those genes (the P gene), through utilization of more than one translation initiation codon and/or the introduction of one or more nontemplated residues to allow access to alternate reading frames, more than one protein is always produced, though the exact number and type of extra proteins vary both between and within genera. The expression of other proteins from overlapping reading frames was first shown in Sendai virus (SeV) (26, 55). SeV (15, 29), and Human parainfluenza virus type 1 (hPIV1) (8) expre...