鸟类白血病病毒亚组J的快速适应性进化,以应对生物技术诱导的宿主耐药性
Magda Matoušková1, Jiří Plachý1, Dana Kučerová1
1Department of Viral and Cellular Genetics, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
PLoS pathogens
|August 15, 2024
概括
通过CRISPR基因编辑,创造了对禽类白血病病毒亚组J (ALV-J) 耐药的. 然而,病毒适应克服这种耐药性,表明需要更复杂的基因修改来实现牲畜中强大的抗病毒策略.
科学领域:
- 动物遗传学 动物遗传学
- 病毒学 病毒学
- 基因组工程是基因组工程.
背景情况:
- 克里斯普尔/Cas9技术使得生殖基因编辑用于牲畜特征修改,包括病毒性疾病耐药性.
- 禽类白血病病毒亚组J (ALV-J) 对家禽健康构成威胁.
- 之前的研究通过CRISPR/Cas9编辑成功产生了ALV-J耐药性的.
研究的目的:
- 研究ALV-J的适应能力,以克服的CRISPR诱导的耐药性.
- 识别病毒突变,使其能够适应修改后的宿主受体.
- 评估不同水平的受体修饰对持久耐药性的有效性.
主要方法:
- 使用CRISPR/Cas9基因组编辑,在的ALV-J受体 (NHE1) 中删除了一个特定的氨基酸 (W38).
- 进行了体外和体内测试,以确认编辑的耐药性.
- 使用逆转录病毒记者测定来选择和识别适应的ALV-J变体.
- 在适应变异的病毒包膜蛋白中测序发现的突变.
- 通过将它们重新引入病毒,确认了已识别的突变的适应能力.
主要成果:
- 在NHE1 (W38-/-) 中具有W38缺失的在体外显示出对ALV-J的耐药性.
- 成功选择了适应ALV-J变体,它们的包膜基因发生了突变.
- 在体外,所有八种已识别的适应性突变都允许病毒在W38-/-细胞中复制.
- 在体内,两个适应变异在W38-/-中引起瘤诱导,这表明部分抗性分解.
- 具有更广泛的受体修饰的仍然对病毒有抗性.
结论:
- 宿主受体的微小修改,如W38删除,可以通过病毒适应来克服.
- 病毒适应主要涉及病毒包膜蛋白的突变.
- 通过基因工程在牲畜中实现强大而持久的抗病毒耐药性,需要比单个氨基酸删除更复杂的遗传修饰.
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