Lopez N, Muller R, Prehaud C, Bouloy M
Laboratoire des Bunyaviridés, Institut Pasteur, Paris, France.
J Virol. 1995 Jul;69(7):3972-9. doi: 10.1128/JVI.69.7.3972-3979.1995.
Overlapping cDNAs representing the complete L segment of Rift Valley fever virus were assembled, and the L protein was expressed via a recombinant vaccinia virus. The transcriptase activity of the L protein was assayed with two types of templates: natural ribonucleoproteins (RNPs) and artificial genome-like RNAs. RNPs purified in a CsCl gradient did not retain the RNA polymerase function, but the activity was restored when the L cDNA was expressed in mammalian cells via a recombinant vaccinia virus. Indeed, after transfection of transcriptase-depleted RNPs in cells infected with the recombinant vaccinia virus expressing the L protein, the mRNAs coding for the N and NSs proteins and to a lesser extent, those coding for the glycoproteins were synthesized as well as the corresponding proteins. The transcriptase activity of the recombinant L protein was then investigated by using synthetic templates containing the reporter chloramphenicol acetyltransferase gene in the antisense orientation flanked by the 3' and 5' noncoding region of the S genomic segment. Our results indicate that after transfection of the RNA templates, transcription was achieved in cells coexpressing both the L and N proteins. Together, the experiments demonstrate that the two proteins N and L are absolutely required and sufficient to reconstitute the transcriptase activity.
构建了代表裂谷热病毒完整L片段的重叠cDNA,并通过重组痘苗病毒表达L蛋白。用两种类型的模板检测L蛋白的转录酶活性:天然核糖核蛋白(RNP)和人工基因组样RNA。在CsCl梯度中纯化的RNP不保留RNA聚合酶功能,但当L cDNA通过重组痘苗病毒在哺乳动物细胞中表达时,活性得以恢复。实际上,在用表达L蛋白的重组痘苗病毒感染的细胞中转染去除转录酶的RNP后,编码N和NSs蛋白的mRNA以及编码糖蛋白的mRNA(程度较低)以及相应的蛋白都被合成了。然后通过使用在反义方向上含有报告氯霉素乙酰转移酶基因且两侧为S基因组片段3'和5'非编码区的合成模板来研究重组L蛋白的转录酶活性。我们的结果表明,转染RNA模板后,在同时共表达L和N蛋白的细胞中实现了转录。总之,这些实验证明N和L这两种蛋白是重构转录酶活性绝对必需且足够的。