Rearrangement of the genes of vesicular stomatitis virus eliminates clinical disease in the natural host: New strategy for vaccine development
Rearrangement of the genes of vesicular stomatitis virus eliminates clinical disease in the natural host: New strategy for vaccine development
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DOI：
10.1128/jvi.75.13.6107-6114.2001
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发表时间：
2001-07-01
影响因子：
5.4
通讯作者：
Wertz, GW
中科院分区：
文献类型：
--
作者：
Flanagan, EB;Zamparo, JM;Wertz, GW
非节段负链RNA病毒的基因表达受与单个转录启动子的距离控制，因此可以通过基因重排系统地操纵这些病毒的表型。我们研究了基因重排的潜力，作为一种手段，开发减毒活疫苗候选人水泡性口炎病毒（VSV）在家猪，这种病毒的天然宿主。结果表明，将核衣壳蛋白基因从单个转录启动子上移开，减弱并最终消除了病毒致病的潜力。将这种变化与表面糖蛋白基因的重新定位相结合，产生了一种疫苗，该疫苗可保护免受野生型VSV的攻击。通过对病毒特性的增量操纵，基因重排提供了一种新的方法来产生针对这类病毒的减毒活疫苗。
Gene expression among the nonsegmented negative-strand RNA viruses is controlled by distance from the single transcriptional promoter, so the phenotypes of these viruses can be systematically manipulated by gene rearrangement. We examined the potential of gene rearrangement as a means to develop live attenuated vaccine candidates against Vesicular stomatitis virus (VSV) in domestic swine, a natural host for this virus. The results showed that moving the nucleocapsid protein gene away from the single transcriptional promoter attenuated and ultimately eliminated the potential of the virus to cause disease. Combining this change with relocation of the surface glycoprotein gene yielded a vaccine that protected against challenge with wild-type VSV. By incremental manipulation of viral properties, gene rearrangement provides a new approach to generating live attenuated vaccines against this class of virus.