保存的非编码RNA基因影响了Simbuviruses的神经病原性:在Schmallenberg病毒模型中的分子剖析
Laura Bonil1, Laetitia Wiggers1, Hélène Dumont1
1Department of Veterinary Medicine, Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit, University of Namur, Namur, Belgium.
PLoS pathogens
|March 10, 2026
概括
施马伦堡病毒的茎环结构和GC信号对于病毒复制和产生至关重要. 这些元素的突变减弱了病毒,减少了病毒毒性和神经病变.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 辛布血清组病毒,包括施马伦堡病毒 (SBV),是导致发烧性疾病和先天性形的树冠病毒.
- 这些病毒具有三部分,负感RNA基因组,没有多元A尾.
- 小基因组段的5' UTR含有保存的RNA元素,如茎环 (SL) 结构和GC信号,可能调节转录和翻译.
研究的目的:
- 研究SL结构和GC信号在SBV复制,转录终止和毒性中的功能.
- 阐明这些cis调节元素在病毒神经病变发生过程中的作用.
主要方法:
- 使用逆转基因系统,制造出具有SL结构和GC信号变化的SBV突变.
- 在细胞培养中评估了复制动力学,转录终止和核体 (N) 蛋白丰度.
- 病毒性和神经病变发生在免疫能力强的小鼠模型中进行了评估.
主要成果:
- SL结构,特别是茎长度,对于SBV生产至关重要;至少需要三个基对进行复制.
- 较短的SL茎减少了病毒适应性,N蛋白水平,并改变了mRNA/基因组RNA比率.
- GC信号突变损害了mRNA终结,限制了N蛋白合成和病毒组合.
- 突变病毒显示病毒载量减少,大脑扩散,并增加了小鼠的生存率.
- 虽然GC信号突变被减弱,但仍保持了活跃的转录.
结论:
- 在SBV中,SL结构和GC信号是关键的cis-regulatory元素.
- 这些元素通过调节病毒复制和神经病变发生来间接决定SBV的毒性.
- 针对这些因素提供了控制SBV和相关病毒的潜在策略.
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