有针对性的病毒适应会产生一种猿类热带性乙型肝炎病毒,该病毒会感染大黄蜂细胞
Yongzhen Liu1, Thomas R Cafiero1, Debby Park1
1Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
Nature communications
|June 16, 2023
概括
研究人员开发了一种新的灵长类动物模型,通过修改病毒以感染大黄蜂来感染乙型肝炎病毒 (HBV) 感染. 这一突破克服了物种障碍,使得慢性病毒性肝炎的更好研究成为可能.
科学领域:
- 病毒学 病毒学
- 肝病学 肝病学是一种肝病学.
- 灵长类动物模型
背景情况:
- 乙型肝炎病毒 (HBV) 感染仅限于人类和黑猩猩,阻碍了慢性病毒性肝炎的研究.
- 非人类灵长类动物感染HBV的一个关键障碍是HBV和猿类甲酸共运输多 (NTCP) 受体之间的不相容性.
研究的目的:
- 为了确定NTCP的关键残留物,负责HBV结合和内部化.
- 建立一个合适的非人类灵长类动物模型来研究HBV感染和慢性病毒性肝炎.
主要方法:
- 从各种灵长类物种 (旧世界子,新世界子,类动物) 选NTCP正确物种,使用突变发生分析.
- 在实验室感染研究中,使用初级马尔莫塞特肝细胞和诱导多能干细胞衍生的肝细胞样细胞.
- 适应的仿真HBV基因组与修改的preS1区域的生成.
主要成果:
- 确定了介导病毒结合和内部化的关键残留物.
- 马尔莫塞特被确定为适合HBV感染的NHP物种.
- 主要和干细胞衍生的马肝细胞都支持HBV和毛HBV (WMHBV) 感染.
- 与野生型HBV相比,适应的仿真HBV基因组在马尔莫塞特肝细胞中表现出更有效的感染.
结论:
- 针对性修改HBV (种类化) 可以克服在小型非人类灵长类动物中感染HBV的物种障碍.
- 这项研究为开发功能性HBV灵长类模型铺平了道路,以便进一步研究病毒性肝炎.
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