Rinderpest Viruses Lacking the C and V Proteins Show Specific Defects in Growth and Transcription of Viral RNAs

Abstract

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...

The C, V and W proteins of Nipah virus inhibit minigenome replication

“…The V proteins of several paramyxoviruses play a role in regulating viral replication. Recombinant paramyxoviruses lacking V proteins, including rinderpest virus (Baron & Barrett, 2000), SeV (Kato et al, 1997b) and MV (Tober et al, 1998), produced increased levels of genomic RNA, mRNA and viral proteins. In addition, the V protein of SeV inhibited the replication of defective interfering particles (Curran et al, 1991;Horikami et al, 1996), and the V protein of SV5 inhibited viral transcription and replication (Lin et al, 2005).…”

“…The sequences of the P proteins of paramyxoviruses are not well conserved (Baron et al, 1993) and, whilst a V protein is not expressed by all paramyxoviruses, the unique carboxylterminal domain of V is more conserved than the aminoterminal domain shared with P (Galinski et al, 1992; Matsuoka et al, 1991;Witko et al, 2006). The C, V and W proteins of paramyxoviruses are known to play multiple roles in the viral life cycle, functioning as interferon antagonists (Didcock et al, 1999;Goodbourn et al, 2000;He et al, 2002;Komatsu et al, 2004;Lin et al, 2005 Shaffer et al, 2003), in addition to regulating viral transcription and replication both in vitro and in vivo (Bankamp et al, 2005;Baron & Barrett, 2000;Curran et al, 1991Curran et al, , 1992Horikami et al, 1996; Kato et al, 1997a, b;Lin et al, 2005;Malur et al, 2004;Parks et al, 2006; Patterson et al, 2000;Reutter et al, 2001;Smallwood & Moyer, 2004;Tober et al, 1998;Witko et al, 2006).As very little is known about the replication of the henipaviruses, the goal of this research was to investigate the roles that the C, V and W proteins of NiV play in viral transcription and replication. Here, we demonstrate that the C, V and W proteins of NiV inhibit NiV minigenome replication.…”

Scientific Opinion on peste des petits ruminants

“…The P gene also encodes the three accessory proteins V, W and C, which are sometimes referred to as non-structural, although it is not conclusively proven that they are not part of the virion. The accessory proteins are not required for the replication and assembly of the virus (Schneider et al, 1997; Baron and Barrett, 2000). The P and L proteins together form the functional viral RNA polymerase.…”

Identification of a Mutation in Editing of Defective Newcastle Disease Virus Recombinants That Modulates P-Gene mRNA Editing and Restores Virus Replication and Pathogenicity in Chicken Embryos

“…The mechanism of the in vivo attenuation was demonstrated to involve the interferon system in which accessory proteins, particularly V or C proteins, inhibit interferon signaling or suppress interferon production (reviewed in references 7 and 8). Additional roles of paramyxovirus accessory proteins in viral RNA transcription and synthesis, as well as in virus assembly and propagation, were also recently uncovered, demonstrating functional versatility of these proteins (1,9,22).The dual function of the V protein of NDV in virus replication, as well as in virus virulence, was shown by generating mutants lacking the entire V and W proteins or only the unique C-terminal part of the V protein or by constructing a mutant expressing low levels of V protein (16). The C terminus of the V protein, which is highly rich in cysteines, is of particular interest since it is conserved in all three genera of paramyxovirinae, with the exception of human parainfluenza virus types 1 and 3 (6, 15).…”