Synergistic roles of the E2 glycoprotein and 3′ untranslated region in the increased genomic stability of chimeric classical swine fever virus with attenuated phenotypes

Synergistic roles of the E2 glycoprotein and 3′ untranslated region in the increased genomic stability of chimeric classical swine fever virus with attenuated phenotypes
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DOI:
10.1007/s00705-017-3427-9
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发表时间:
2017-09-01
影响因子:
2.7
通讯作者:
Pan, Zishu
Pan, Zishu
中科院分区:
医学4区
文献类型:
--
作者:
Wu, Rui;Li, Ling;Pan, Zishu

文献摘要

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猪瘟病毒 (CSFV) 的 E2 糖蛋白和 3' 非翻译区 (UTR) 是毒力决定因素。为了研究E2和3'UTR在致病性和基因组稳定性方面的协同作用,利用反向遗传方法,通过将强毒CSFV石门株的E2基因和/或3'UTR替换为兔子化“中国”株(C株)的相应序列,构建了一系列嵌合CSFV。研究了嵌合 CSFV 的体外生长特征和体内致病性。我们的结果表明,E2 糖蛋白介导病毒细胞间传播和病毒颗粒释放,并且 3'UTR 调节病毒 RNA 复制。 CSFV E2 和 3'UTR 协同调节感染性病毒的产生、体外病毒基因组稳定性以及猪体内的减毒。这项工作有助于我们了解猪瘟病毒基因组的结构和功能以及病毒致病性,并将有助于开发新型猪瘟疫苗。
The E2 glycoprotein and 3' untranslated region (UTR) of classical swine fever virus (CSFV) are virulence determinants. To investigate the synergistic roles of E2 and 3'UTR for pathogenicity and genomic stability, a series of chimeric CSFVs were constructed by replacing the E2 gene and/or 3'UTR of virulent CSFV strain Shimen with the corresponding sequence of the lapinized 'Chinese' strain (C-strain) using a reverse genetic approach. The in vitro growth characterization and in vivo pathogenicity of the chimeric CSFVs were investigated. Our results demonstrated that the E2 glycoprotein mediates virus cell-to-cell spread and viral particle release and that the 3'UTR regulates viral RNA replication. The CSFV E2 and 3'UTR synergistically modulate infectious virus production, viral genomic stability in vitro, and attenuation in swine. This work contributes to our understanding of the structure and function of the CSFV genome and virus pathogenicity and will be useful for the development of a novel CSF vaccine.