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在寨卡病毒感染后,胎盘自和病毒复制在人类和非人类灵长类胎盘中同定位:对治疗干预的含义

Jennifer R McKinney¹, Maxim D Seferovic¹, Angela M Major²

¹Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, United States.

Frontiers in virology (Lausanne, Switzerland)

|July 11, 2023

概括

寨卡病毒 (ZIKV) 感染会扰乱胎盘中的自,在人类和非人类灵长类动物模型中观察到关键的自基因的表达减少. 这一发现对于理解ZIKV垂直传播和定时治疗干预措施至关重要.

科学领域:

病毒学病毒学
细胞生物学细胞生物学
免疫学免疫学免疫学

背景情况:

自在寨卡病毒 (ZIKV) 感染中的作用受到争论,研究表明诱导和抑制.
在人类和非人类灵长类动物模型中缺乏现场数据,阻碍了对ZIKV垂直传播的理解.
正在探索自抑制剂作为对抗ZIKV和其他RNA病毒的潜在治疗方法.

研究的目的:

调查胎盘ZIKV感染和自之间的细胞,空间和时间关联.
评估人类初级细胞培养和先天性ZIKV感染病例中的自标志物.
在ZIKV感染的实验性非人类灵长类动物 () 模型中评估自.

主要方法:

主要的人类热囊细胞在体外感染了ZIKV,并通过qPCR分析了自基因表达.
在现场杂交 (ISH) 和免疫组织化学被用来检查人体和鼠胎盘组织中的自基因和蛋白质标记物.
在ZIKV感染和未感染的胎盘小体中量化自蛋白标记物 (LC3B,p62/SQSTM1).

主要成果:

齐克病毒感染导致人体热原体中自基因ATG5和p62/SQSTM1的表达减少.
在现场检查显示,自标记物和ZIKV感染在人类先天性病例和鸟组织之间的空间关联.
在ZIKV感染的鱼胎盘小体中观察到LC3B和p62/SQSTM1的显著减少表达.

结论:

自失调,特别是下调,伴随着ZIKV在灵长类胎盘中的复制.
这些发现为ZIKV治疗中自调节时间的重要性提供了有关灵长类动物模型中的第一个现场证据.
这项研究对理解和治疗其他垂直传播的RNA病毒有意义,突出显示了自失调在怀孕中的作用.

关键词:

寨卡病毒寨卡病毒自自是自的过程.自和病毒感染.遗传性寨卡综合征是一种先天性寨卡综合征.胎盘病毒感染胎盘病毒感染病毒传播病毒传播病毒传播

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