The paramyxovirus polymerase complex as a target for next-generation anti-paramyxovirus therapeutics
DNA fragments complementary to the genome of an avirulent strain (AVO1) of the rabies virus were cloned and sequenced. The sequence of the 3386 nucleotides from the 3' end covers the genes encoding the leader RNA, the nucleoprotein N, the phosphoprotein M1 and the matrix protein M2, as well as the intergenic regions. Comparison of the AVO1 sequence with those of other rabies strains reveals a very high conservation at both the nucleotide and the amino acid levels. The non-protein coding regions of the genome (leader gene, untranslated regions flanking mRNAs, untranscribed intergenic regions) are discussed in terms of their possible involvement in the rabies virus biology. Comparison of the rabies genome with those of other unsegmented negative strand RNA viruses (rhabdoviruses and paramyxoviruses) indicates that the start and stop transcription signals, located at the border of each gene encoding a protein, and the regions of the phosphoprotein and matrix proteins that could be implicated in the transcription process, retain a similar overall structure. Thus, it appears that during evolution, these virus genomes have diverged while keeping the protein structures and regulatory sequence important in transcription. These results prompt us to propose that the major distinctive feature of the rabies transcription may arise from the highly variable intergenic regions where the attenuation of transcription is assumed to take place.