肝炎E ORF2 阻断热囊细胞自引发流产通过LC3B结合而不是PI3K/Akt/mTOR路径抑制
Yinzhu Chen1, Yifei Yang2, Qianyu Bai1
1State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Microorganisms
|January 28, 2026
概括
肝炎E病毒ORF2蛋白通过直接结合LC3B来抑制胎盘细胞的自,导致流产. 这一发现澄清了HEV诱导的生殖损伤背后的分子机制.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 生殖免疫学 生殖免疫学
背景情况:
- 肝炎E病毒 (HEV) 是一种与流产等不良妊娠结果相关的动物性病原体.
- 以前的研究表明,HEV基因型3 (HEV-3) 损害了胎盘细胞的自流,但具体机制尚不清楚.
研究的目的:
- 阐明HEV抑制人类热原体细胞 (JEG-3) 中自的分子机制.
- 确定负责自抑制的特定HEV蛋白质及其与自机械的相互作用.
主要方法:
- 在JEG-3细胞中,HEVORF2和ORF3蛋白过度表达.
- 西部涂抹 (WB) 和RT-qPCR用于分析蛋白质和基因表达.
- 共同定位研究,AlphaFold 3预测和共同免疫沉以评估蛋白质相互作用.
主要成果:
- HEV ORF2,而不是ORF3,通过降低LC3B水平和积累p62.2,显著抑制了自.
- ORF2抑制了PI3K/Akt/mTOR通路,增强了TFEB核转位,并诱导了AMPK酸化.
- 证实了HEV ORF2和LC3B之间的直接物理相互作用,阻断了自细胞形成.
结论:
- HEV ORF2是关键的病毒蛋白质,通过直接结合LC3B,抑制了热囊细胞的自.
- 这种相互作用破坏了自细胞形成,为HEV相关流产提供了分子解释.
- 这些发现为HEV诱导的生殖损伤和潜在的治疗点提供了新的见解.
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