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脊髓灰质炎病毒在成熟的hiPSC衍生的神经球体中复制了其免疫逃避行为

Jonas Govaerts^1,2,3, Elise Van Breedam¹, Sarah De Beuckeleer^1,4,5

¹Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium.

Frontiers in immunology

|October 1, 2024

概括

与其他病毒不同,疹病毒 (VZV) 在人类神经模型中逃避免疫检测. 这项研究揭示了VZVV.

科学领域:

神经科学是一个神经科学.
免疫学免疫学免疫学
病毒学病毒学

背景情况:

脊髓灰质炎病毒 (VZV) 可以导致严重的中枢神经系统 (CNS) 并发症,如脑炎和脑膜炎.
第一种类型的干扰素 (IFN) 信号传递对于对外围组织病毒感染的先天免疫防御至关重要.

研究的目的:

在类似于人类神经系统的环境中研究对VZV的先天免疫反应.
描述VZV在中枢神经系统中的免疫逃避机制.

主要方法:

建立并成熟的5个月大的人类诱导多能干细胞 (hiPSC) 衍生神经球体 (NSPHs) 含有神经元和星体.
作为阳性对照,感染了VZV (VZV^eGFP-ORF23) 和仙台病毒 (SeV^eGFP) 的记者菌株的NSPH.
利用活细胞成像,免疫细胞化学和NanoString数字转录学来分析病毒感染和宿主免疫反应.

主要成果:

VZV^eGFP-ORF23感染了整个NSPH,而SeV^eGFP感染是局部的.
SeV触发了强大的I型IFN反应,而VZV感染抑制了IFN信号传递,抗原呈现基因 (IL-6,CXCL10,CD74) 和抗病毒蛋白表达.
VZV^eGFP-ORF23感染导致压力颗粒的形成和细胞完整性的破坏,尽管明显的免疫逃避.

结论:

由hiPSC衍生的神经球体对SeV表现出功能性天生的免疫反应,但在神经环境中展示了VZV强大的免疫逃避能力.
由于VZV能够抑制神经细胞中的先天免疫力,因此可能导致中枢神经系统并发症.

关键词:

抗原呈现的呈现方式.人类的 iPScSc.神经球体类神经球体.压力颗粒是压力颗粒.结构完整性的结构完整性.第一种类型的干扰子信号传输.疹病毒-疹病毒病毒.

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