Genetic polymorphism in the rabies virus nucleoprotein gene

In an attempt to compare intrinsic and extrinsic genetic diversity of the lyssavirus genotypes, 69 rabies virus isolates from various part of the world were partially sequenced and compared to 13 representative isolates of the 6 lyssavirus genotypes. The analysis of their phylogenetic relationships, performed on the complete nucleoprotein (N) coding gene (1350 bases), established that the rabies virus isolates all belonged to genotype 1 and that at least 11 phylogenetic lineages could be identified in accordance with their geographical localization and species of origin. These lineages diverged mostly by the accumulation of synonymous mutations. Stabilizing selection, possibly related to host specificity, limits amino acid sequence and antigenic drift. Analyses were also performed either on the highly variable 400-base region coding for the amino terminus of the N protein or on the 93-base noncoding region corresponding to the 3' end of the N mRNA, the intergenic N-phosphoprotein (M1) region, and the 5' end of the M1 mRNA. These shorter nucleotide sequences were shown to provide phylogenetic data suitable for the completion of large epidemiological studies, but with less robustness. This latter noncoding sequence, despite a 3.1 times higher mutation rate than its adjacent coding N gene, followed a parallel evolutionary pattern.