Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach
Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach
复制标题
DOI：
10.3109/13550280009018301
复制
发表时间：
2000-10-01
影响因子：
3.2
通讯作者：
Dietzschold, B
中科院分区：
文献类型：
--
作者：
Morimoto, K;Foley, HD;Dietzschold, B
将高神经侵入性和嗜神经性毒株SHBRV-18、CVS-N2c和CVS-B2c的狂犬病毒糖蛋白(G)基因导入无神经侵入性和嗜神经性较低的SN-10毒株，进一步探讨G在狂犬病发病机制中的作用。重组病毒的表型分析显示，正如预期的那样，一种特定狂犬病毒毒株的嗜神经性是其G的功能。然而，在每种情况下，重组病毒的致病性都明显低于野生型病毒，这表明虽然G决定了嗜神经性，但其他病毒属性在发病机制中也很重要。重组病毒的低致病性至少部分是由于转录活性的强烈增加。另一方面，与SHBRV-18野生型病毒感染细胞相比，重组R-SHB18病毒感染细胞产生感染性病毒的时间明显延迟。将r - shb18g细胞质结构域、跨膜结构域和茎区替换为sn - 10g既不能显著提高出芽效率，也不能提高致病性。这些结果表明，G的胞质结构域与基质蛋白的最佳匹配可能不足以获得最大的病毒出芽效率，而出芽效率显然是病毒致病性的一个主要因素。我们的研究表明，为了保持狂犬病病毒的致病性，必须高度保守病毒各结构元件之间的相互作用，并严格控制病毒蛋白，特别是G蛋白的表达。
The rabies virus glycoprotein (G) gene of the highly neuroinvasive and neurotropic strains SHBRV-18, CVS-N2c, and CVS-B2c was introduced into the non-neuroinvasive and less neurotropic SN-10 strain to provide further insight into the role of G in the pathogenesis of rabies. Phenotypic analyses of the recombinant viruses revealed, as expected, that the neurotropism of a particular rabies virus strain was a function of its G. Nevertheless, the pathogenicity of the recombinant viruses was, in every case, markedly lower than that of the wild-type viruses suggesting that while the G dictates neurotropism, other viral attributes are also important in pathogenesis. The low pathogenicity of the recombinant viruses is at least in part due to a strong increase in transcription activity. On the other hand, the production of infectious virus by the R-SHB18 recombinant virus-infected cells was significantly delayed by comparison with SHBRV-18 wild-type virus infected-cells. Replacement of the R-SHB18 G cytoplasmic domain, transmembrane domain, and stem region with its SN-10 G counterparts neither results in a significant increase in budding efficiency nor an increase in pathogenicity. These results suggest that an optimal match of the cytoplasmic domain of G with the matrix protein may not be sufficient for maximal virus budding efficiency, which is evidently a major factor of virus pathogenicity. Our studies indicate that to maintain pathogenicity, the interactions between various structural elements of rabies virus must be highly conserved and the expression of viral proteins, in particular the G protein, must be strictly controlled.