以HAVCR1为中心的宿主因子网络驱动着寨卡病毒的垂直传播
Wenzhe Yu1, Jun Tao1, Hongmin Cao1
1Fujian Provincial Key Laboratory of Reproductive Health Research, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, Fujian, China.
Cell reports
|March 29, 2025
概括
肝炎A病毒细胞受体1 (HAVCR1) 是寨卡病毒 (ZIKV) 胎盘传播的关键因素. 向HAVCR1可以预防先天性寨卡综合征和相关的妊娠并发症.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 寨卡病毒 (ZIKV) 的垂直传播会导致严重的先天性形.
- 能够使ZIKV从母亲传播到胎儿的特定宿主因素尚未完全理解.
研究的目的:
- 为了确定参与ZIKV感染的胎盘内在因素.
- 为了阐明ZIKV进入胎盘细胞的机制.
主要方法:
- 用全基因组的CRISPR查来识别宿主因素.
- 在胎盘 trofhoblasts 中分析了 HAVCR1 的功能.
- 在小鼠中进行了胎盘特异的 Havcr1 删除.
- 机理学研究涉及蛋白质-蛋白质相互作用和内细胞化试验.
主要成果:
- 肝炎A病毒细胞受体1 (HAVCR1) 被确定为胎盘 trofhoblasts 中的主要ZIKV受体.
- GATA3-HAVCR1轴影响胎盘中的ZIKV细胞热流.
- 在小鼠胎盘中删除Havcr1显著降低了ZIKV传播和不良妊娠结果.
- HAVCR1通过其免疫球蛋白类变量域与ZIKV结合,与病毒包膜蛋白和氨酸蛋白相互作用.
- 发现AP2S1与HAVCR1合作,通过克拉斯林介导的内细胞分裂来实现ZIKV内部化.
结论:
- HAVCR1在ZIKV垂直传输中起着关键作用.
- HAVCR1代表了预防先天性寨卡综合征的潜在治疗标.
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