Rabies virus quasispecies: Implications for pathogenesis
Rabies virus quasispecies: Implications for pathogenesis
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DOI：
10.1073/pnas.95.6.3152
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发表时间：
1998-03-17
影响因子：
11.1
通讯作者：
Dietzschold, B
中科院分区：
文献类型：
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作者：
Morimoto, K;Hooper, DC;Dietzschold, B
小鼠适应性狂犬病病毒株CVS-24（其中CVS是攻毒病毒标准品）在BHK细胞中传代导致快速选择命名为CVS-B2c的显性变体，其在基因型和表型上与小鼠脑细胞或神经母细胞瘤细胞传代CVS-24中存在的显性变体CVS-N2 c不同。CVS-B2c的糖蛋白与CVS-N2 c的糖蛋白相比有10个氨基酸的替换。由于CVS-B2 e在BHK细胞中可重复选择，因此它可能是CVS-24的保守亚群，CVS-N2 c在体外和体内比CVS-B2c更嗜神经，CVS-B2c在体外和体内更容易在非神经细胞中复制。这些特征似乎与两种变体的致病性有关。CVS-N2 c比CVS-B2c对成年小鼠的致病性更高。相反，CVS-B2c对新生小鼠的致病性更高。当CVS-N2 c和CVS-B2c的混合物用于感染新生和成年小鼠时，这些致病性的差异反映在选择模式中。尽管CVS-N2 c在成年小鼠中被高度选择，但在新生小鼠中没有发现任何变异体的选择，这表明发育的某些方面，如神经和免疫系统的成熟，可能有助于选择过程。我们推测，狂犬病病毒株内不同变异体的存在可能有助于病毒克服宿主内和物种间传播的障碍。
Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically and phenotypically from the dominant variant CVS-N2c present in mouse-brain- or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVS-B2c has 10 amino acid substitutions compared with that of CVS-N2c, Because CVS-B2e can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24, CVS-N2c is more neurotropic in vitro and in vivo than CVS-B2c, which replicates more readily in nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is more pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is more pathogenic for neonatal mice. These differences in pathogenicity are reflected in the selection pattern when mixtures of CVS-N2c and CVS-B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was seen in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the selection process. We speculate that the existence of different variants within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species.