Badrane H, Bahloul C, Perrin P, Tordo N
Laboratoire des Lyssavirus, Department of Virology, Institut Pasteur, Paris, France.
J Virol. 2001 Apr;75(7):3268-76. doi: 10.1128/JVI.75.7.3268-3276.2001.
The genetic diversity of representative members of the Lyssavirus genus (rabies and rabies-related viruses) was evaluated using the gene encoding the transmembrane glycoprotein involved in the virus-host interaction, immunogenicity, and pathogenicity. Phylogenetic analysis distinguished seven genotypes, which could be divided into two major phylogroups having the highest bootstrap values. Phylogroup I comprises the worldwide genotype 1 (classic Rabies virus), the European bat lyssavirus (EBL) genotypes 5 (EBL1) and 6 (EBL2), the African genotype 4 (Duvenhage virus), and the Australian bat lyssavirus genotype 7. Phylogroup II comprises the divergent African genotypes 2 (Lagos bat virus) and 3 (Mokola virus). We studied immunogenic and pathogenic properties to investigate the biological significance of this phylogenetic grouping. Viruses from phylogroup I (Rabies virus and EBL1) were found to be pathogenic for mice when injected by the intracerebral or the intramuscular route, whereas viruses from phylogroup II (Mokola and Lagos bat viruses) were only pathogenic by the intracerebral route. We showed that the glycoprotein R333 residue essential for virulence was naturally replaced by a D333 in the phylogroup II viruses, likely resulting in their attenuated pathogenicity. Moreover, cross-neutralization distinguished the same phylogroups. Within each phylogroup, the amino acid sequence of the glycoprotein ectodomain was at least 74% identical, and antiglycoprotein virus-neutralizing antibodies displayed cross-neutralization. Between phylogroups, the identity was less than 64.5% and the cross-neutralization was absent, explaining why the classical rabies vaccines (phylogroup I) cannot protect against lyssaviruses from phylogroup II. Our tree-axial analysis divided lyssaviruses into two phylogroups that more closely reflect their biological characteristics than previous serotypes and genotypes.
利用编码参与病毒 - 宿主相互作用、免疫原性和致病性的跨膜糖蛋白的基因，对狂犬病病毒属（狂犬病病毒和狂犬病相关病毒）代表性成员的遗传多样性进行了评估。系统发育分析区分出7种基因型，可分为两个具有最高自展值的主要系统发育组。系统发育组I包括全球基因型1（经典狂犬病病毒）、欧洲蝙蝠狂犬病病毒（EBL）基因型5（EBL1）和6（EBL2）、非洲基因型4（杜文黑格病毒）以及澳大利亚蝙蝠狂犬病病毒基因型7。系统发育组II包括不同的非洲基因型2（拉各斯蝙蝠病毒）和3（莫科拉病毒）。我们研究了免疫原性和致病性特性，以探讨这种系统发育分组的生物学意义。发现系统发育组I的病毒（狂犬病病毒和EBL1）通过脑内或肌肉注射途径对小鼠具有致病性，而系统发育组II的病毒（莫科拉病毒和拉各斯蝙蝠病毒）仅通过脑内途径具有致病性。我们表明，毒力所必需的糖蛋白R333残基在系统发育组II的病毒中自然地被D333取代，这可能导致其致病性减弱。此外，交叉中和区分出了相同的系统发育组。在每个系统发育组内，糖蛋白胞外域的氨基酸序列至少有74%相同，抗糖蛋白病毒中和抗体表现出交叉中和。在系统发育组之间，同一性小于64.5%且不存在交叉中和，这解释了为什么经典狂犬病疫苗（系统发育组I）不能预防系统发育组II的狂犬病病毒。我们的树轴分析将狂犬病病毒分为两个系统发育组，与先前的血清型和基因型相比，这两个组更能紧密反映它们的生物学特性。
