Abstract
The P gene of paramyxoviruses is unique in producing not only P but also “accessory” C and/or V proteins. Successful generation of C- or V-deficient recombinant viruses using a reverse genetics technique has been revealing their importance in viral pathogenesis as well as replication. As for Sendai virus (SeV), the C proteins, a nested set of four polypeptides C’, C, Y1, and Y2, have been shown to exert multiple functions in escaping from the host innate immunity, inhibiting virus-induced apoptosis, promoting virus assembly and budding, and regulating viral RNA synthesis. In this study, we subjected the 4C(-) recombinant lacking expression of all four C proteins to serial passages through eggs, and found the rapid emergence of a C-recovered revertant virus. Unlike the SeV strains or the recombinants reported previously or tested in this study, this was caused by an exceptionally quick accumulation of U-to-C transitions in a limited region of the 4C(-) genome causing recovery of the C protein expression. These results suggest that a lack of C proteins could lead unexpectedly to strong selective pressures, and that the C proteins might play more critical roles in SeV replication than ever reported.
Highlights
Sendai virus (SeV; mouse parainfluenza virus type 1) is a prototype of the family Paramyxoviridae of the order Mononegavirales including some of the most important and ubiquitous diseasecausing viruses of humans and animals, such as parainfluenza viruses, measles virus, mumps virus, Hendra virus, Nipah virus, human metapneumovirus, Newcastle disease virus, canine distemper virus, and rinderpest virus
The P gene of paramyxoviruses is a notable exception, because it produces more than one polypeptide species by means of overlapping frames and by a process known as RNA editing of insertion of nucleotides into the transcript at a specific position during the transcription process [2]
The 4C(-) recombinant virus was generated by introducing several amino acid substitutions within the C proteins without changing of the P polypeptide (Fig. 1; [7])
Summary
Sendai virus (SeV; mouse parainfluenza virus type 1) is a prototype of the family Paramyxoviridae of the order Mononegavirales including some of the most important and ubiquitous diseasecausing viruses of humans and animals, such as parainfluenza viruses, measles virus, mumps virus, Hendra virus, Nipah virus, human metapneumovirus, Newcastle disease virus, canine distemper virus, and rinderpest virus. The gene expression is usually monocistronic, generating a single mRNA, which directs a single translation product. The P gene of paramyxoviruses is a notable exception, because it produces more than one polypeptide species by means of overlapping frames and by a process known as RNA editing of insertion of nucleotides into the transcript at a specific position during the transcription process [2]. The SeV P gene is the most diverse of those of paramyxoviruses, with at least seven polypeptides expressed from it. In addition to P protein, four C proteins (C’, C, Y1, and Y2) are translated from start codons in the +1 reading frame relative to the P open reading frame (ORF), and proteins V and W are produced from the altered P ORF with insertion of one or two G residues by RNA editing, respectively [2]
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