Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity
Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity
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DOI：
10.1128/jvi.75.7.3268-3276.2001
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发表时间：
2001-04-01
影响因子：
5.4
通讯作者：
Tordo, N
中科院分区：
文献类型：
--
作者：
Badrane, H;Bahloul, C;Tordo, N
使用编码参与病毒-宿主相互作用、免疫原性和致病性的跨膜糖蛋白的基因评估了狂犬病病毒属代表性成员（狂犬病和狂犬病相关病毒）的遗传多样性。系统发育分析区分了七种基因型，可分为具有最高引导值的两个主要系统群。系统群 I 包括全球基因型 1（经典狂犬病病毒）、欧洲蝙蝠狂犬病毒 (EBL) 基因型 5 (EBL1) 和 6 (EBL2)、非洲基因型 4（杜文哈奇病毒）和澳大利亚蝙蝠狂犬病病毒基因型 7，系统群 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特性，以研究这种系统发育分组的生物学意义。研究发现，系统群 I 的病毒（狂犬病病毒和 EBL1）通过脑内或肌内途径注射时对小鼠具有致病性，而系统群 II 的病毒（莫科拉和拉各斯蝙蝠病毒）仅通过脑内途径致病。我们发现，在系统群 II 病毒中，毒力所必需的糖蛋白 R333 残基自然被 D333 取代，这可能导致其致病性减弱。此外，交叉中和区分了相同的系统群。在每个系统群内，糖蛋白胞外域的氨基酸序列至少有 74% 相同，并且抗糖蛋白病毒中和抗体表现出交叉中和作用。系统群之间的同一性低于 64.5%，并且不存在交叉中和，这解释了为什么经典狂犬病疫苗（系统群 I）不能预防来自系统群 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群，比以前的血清型和基因型更能反映其生物学特征。
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.