Kissi B, Tordo N, Bourhy H
Unité de la Rage, Institut Pasteur, Paris, France.
Virology. 1995 Jun 1;209(2):526-37. doi: 10.1006/viro.1995.1285.
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.
为了比较狂犬病病毒基因型的内在和外在遗传多样性，对来自世界各地的69株狂犬病病毒分离株进行了部分测序，并与6种狂犬病病毒基因型的13株代表性分离株进行了比较。对其完整核蛋白（N）编码基因（1350个碱基）进行系统发育关系分析，结果表明，狂犬病病毒分离株均属于基因型1，并且根据其地理定位和来源物种，至少可以识别出11个系统发育谱系。这些谱系的差异主要是由于同义突变的积累。可能与宿主特异性相关的稳定选择限制了氨基酸序列和抗原漂移。还对编码N蛋白氨基末端的高度可变400碱基区域、对应于N mRNA 3'端的93碱基非编码区域、基因间N-磷蛋白（M1）区域以及M1 mRNA的5'端进行了分析。这些较短的核苷酸序列显示出能够提供适合大规模流行病学研究的系统发育数据，但稳健性较差。后一种非编码序列尽管突变率比其相邻的编码N基因高3.倍，但遵循平行进化模式。
