Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus.
Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus.
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通过假回复恢复糖蛋白 Erns 二聚化可部分恢复猪瘟病毒的毒力
DOI：
10.1099/jgv.0.000990
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Meyers G
中科院分区：
文献类型：
--
作者：
Tucakov AK;Yavuz S;Schürmann EM;Mischler M;Klingebeil A;Meyers G
猪瘟病毒（classical swine fever virus，CSFV）是猪的重要病原之一。CSFV糖蛋白Erns是一种重要的结构蛋白和毒力因子。后者依赖于这种包膜蛋白的RNA酶活性，并且最有可能是其从感染细胞中分泌。关于其作为毒力因子的功能的另一个重要特征是在病毒感染的细胞和病毒体中发现的二硫键连接的Ernshomodimer的形成。发现缺乏半胱氨酸（Cys）171（负责分子间二硫键形成的残基）的突变体CSFV在猪中减毒（Tews BA，Schürmann EM，Meyers G.J Virol 2009;83：4823-4834）。在用这种二聚化阴性CSFV突变体进行动物实验的过程中，从含有丝氨酸（Ser）209突变为Cys的猪中重新分离病毒。该突变恢复了形成二硫键连接的Ernshomodimer的能力。在瞬时表达研究中，发现携带S209 C变化的Ernsmutants以约wt效率形成同源二聚体。突变蛋白的分泌水平也与野生型Erns相当。与Cys 171 Ser突变体相比，含有Cys 171 Ser/Ser 209 Cys构型的病毒突变体表现出wt生长速率和增加的毒力。这些结果进一步支持了CSFV毒力与Erns二聚化之间的联系。
The classical swine fever virus (CSFV) represents one of the most important pathogens of swine. The CSFV glycoprotein Ernsis an essential structural protein and an important virulence factor. The latter is dependent on the RNase activity of this envelope protein and, most likely, its secretion from the infected cell. A further important feature with regard to its function as a virulence factor is the formation of disulfide-linked Ernshomodimers that are found in virus-infected cells and virions. Mutant CSFV lacking cysteine (Cys) 171, the residue responsible for intermolecular disulfide bond formation, were found to be attenuated in pigs (Tews BA, Schürmann EM, Meyers G.J Virol2009;83:4823–4834). In the course of an animal experiment with such a dimerization-negative CSFV mutant, viruses were reisolated from pigs that contained a mutation of serine (Ser) 209 to Cys. This mutation restored the ability to form disulphide-linked Ernshomodimers. In transient expression studies Ernsmutants carrying the S209C change were found to form homodimers with about wt efficiency. Also the secretion level of the mutated proteins was equivalent to that of wt Erns. Virus mutants containing the Cys171Ser/Ser209Cys configuration exhibited wt growth rates and increased virulence when compared with the Cys171Ser mutant. These results provide further support for the connection between CSFV virulence and Ernsdimerization.
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影响因子：
4.8
作者：
Tews, Birke Andrea;Meyers, Gregor
通讯作者：
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影响因子：
3.7
作者：
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6.7
作者：
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影响因子：
5.4
作者：
B. Tews;Eva-Maria Schürmann;G. Meyers
通讯作者：
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影响因子：
3.7
作者：
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