Mutation of Cysteine 171 of Pestivirus Erns RNase Prevents Homodimer Formation and Leads to Attenuation of Classical Swine Fever Virus
Mutation of Cysteine 171 of Pestivirus Erns RNase Prevents Homodimer Formation and Leads to Attenuation of Classical Swine Fever Virus
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DOI：
10.1128/jvi.01710-08
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发表时间：
2009-03
影响因子：
5.4
通讯作者：
B. Tews;Eva-Maria Schürmann;G. Meyers
中科院分区：
文献类型：
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作者：
B. Tews;Eva-Maria Schürmann;G. Meyers
鼠疫病毒是农场动物的重要病原体，它们进化出独特的策略和功能来留在宿主群体中。Erns是鼠疫病毒的一种结构糖蛋白，具有rna酶活性，是鼠疫病毒的一个毒力因子。Erns在病毒粒子和病毒感染的细胞中形成二硫连接的同型二聚体。在共沉淀和天然蛋白凝胶电泳分析中，参与分子间二硫键形成的残基——半胱氨酸171的突变或缺失会导致二聚化的丧失。然而，在组织培养中可以恢复影响半胱氨酸密码子171的稳定病毒突变体。这些突变体的生长几乎和亲本病毒一样好，并表现出rnase阳性表型。经典猪瘟病毒的二聚体阴性突变体在猪身上被发现是减毒的，尽管该病毒在动物身上明显复制并诱导了显著的中和抗体反应。
ABSTRACT Pestiviruses represent important pathogens of farm animals that have evolved unique strategies and functions to stay within their host populations. Erns, a structural glycoprotein of pestiviruses, exhibits RNase activity and represents a virulence factor of the viruses. Erns forms disulfide linked homodimers that are found in virions and virus-infected cells. Mutation or deletion of cysteine 171, the residue engaged in intermolecular disulfide bond formation, results in loss of dimerization as tested in coprecipitation and native protein gel electrophoresis analyses. Nevertheless, stable virus mutants with changes affecting cysteine codon 171 could be recovered in tissue culture. These mutants grew almost as well as the parental viruses and exhibited an RNase-positive phenotype. Erns dimerization-negative mutants of classical swine fever virus were found to be attenuated in pigs even though the virus clearly replicated and induced a significant neutralizing antibody response in the animals.