Rinderpest viruses lacking the C and V proteins show specific defects in growth and transcription of viral RNAs

Rinderpest viruses lacking the C and V proteins show specific defects in growth and transcription of viral RNAs
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DOI:
10.1128/jvi.74.6.2603-2611.2000
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发表时间:
2000-03-01
影响因子:
5.4
通讯作者:
Barrett, T
Barrett, T
中科院分区:
医学2区
文献类型:
--
作者:
Baron, MD;Barrett, T

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牛瘟病毒是一种麻疹病毒,是牛和野生牛科动物的重要疾病的病原体。所有麻疹病毒的P基因除了产生P蛋白本身外,还产生两种蛋白:在第二个开放阅读框中使用一个替代的起始翻译位点,产生C蛋白,而在共转录下插入一个额外的碱基,产生V蛋白,这是P的氨基末端的一半与一个短的、高度保守的、富含半胱氨酸的锌结合结构域的融合。关于这两种蛋白在牛瘟病毒生命周期中的功能知之甚少。我们已经构建了重组牛瘟病毒,其中这些蛋白质的表达已被抑制,单独和一起,并研究了这些病毒在组织培养中的复制。我们发现,V蛋白的缺乏对病毒的复制率几乎没有影响,但确实导致基因组和反基因组RNA的合成增加,以及细胞病变效应向合胞体形成表型的变化。另一方面,不表达C蛋白的病毒在所有测试的细胞系中明显存在生长缺陷,并且该缺陷似乎与来自病毒基因的mRNA转录减少有关。两种单个突变病毒类型的表型均在既不表达V也不表达C的双突变体中表达。
Rinderpest virus is a morbillivirus and the causative agent of an important disease of cattle and wild bovids. The P genes of all morbilliviruses give rise to two proteins in addition to the P protein itself: use of an alternate start translation site, in a second open reading frame, gives rise to the C protein, while cotranscriptional insertion of an extra base gives rise to the V protein, a fusion of the amino-terminal half of P to a short, highly conserved, cysteine-rich zinc binding domain. Little is known about the function of either of these two proteins in the rinderpest virus life cycle. We have constructed recombinant rinderpest viruses in which the expression of these proteins has been suppressed, individually and together, and studied the replication of these viruses in tissue culture. We show that the absence of the V protein has little effect on the replication rate of the virus but does lead to an increase in synthesis of genome and antigenome RNAs and a change in cytopathic effect to a more syncytium-forming phenotype. Virus that does not express the C protein, on the other hand, is clearly defective in growth in all cell lines tested, and this defect appears to be related to a decreased transcription of mRNA from viral genes. The phenotypes of both individual mutant virus types are both expressed in the double mutant expressing neither V nor C.