干扰素独立的过程限制了麻疹病毒在人类呼吸道原发性上皮细胞中细胞间的传播
Lorellin A Durnell1, Camilla E Hippee1, Roberto Cattaneo2
1Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa , Iowa City, Iowa, USA.
Microbiology spectrum
|September 19, 2023
概括
麻疹病毒 (MeV) 在人体呼吸道上皮质中细胞间的传播不会被干扰素信号制止. 相反,MeV传播受到干扰素独立机制的限制,这有助于其高传染性.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 呼吸系统医学 呼吸系统医学
背景情况:
- 人类呼吸道上皮质中麻疹病毒 (MeV) 放大是其高传染性至关重要的.
- 细胞间传播的MeV在人类呼吸道上皮细胞 (HAE) 中形成感染中心,但这种传播最终被阻止.
- 在HAE中限制MeV传播的机制,特别是干扰子 (IFN) 的作用,尚未完全理解.
研究的目的:
- 研究I型和III型干扰素 (IFN) 在 HAE培养中阻止MeV细胞间传播中的作用.
- 为了确定MeV V蛋白与先天性免疫成分的相互作用是否会影响HAE中的IFN反应.
- 阐明在HAE.中限制MeV传染中心生长的基础机制.
主要方法:
- 利用人类呼吸道上皮细胞 (HAE) 的分化良好的初级培养来模拟MeV感染.
- 服用I型 (IFN-β) 和III型 (IFN-λ1) IFN和阻断IFN受体信号,以评估它们对MeV传播的影响.
- 感染了缺乏V蛋白的MeV突变体的HAE,并使用深度测序,qRT-PCR和单细胞RNA-seq.分析了先天免疫反应.
主要成果:
- 添加IFN-β和IFN-λ1减缓了MeV感染中心的生长,但阻断IFN受体信号传递并没有影响感染中心的大小.
- 阻断I型IFN受体信号传递增强的呼吸道同胞病毒在HAE中传播.
- 对V蛋白缺陷的MeV突变引起了意想不到的突变天生的免疫反应,观察到最小的IFN和IFN刺激的基因转录.
结论:
- IFN信号传递可以有助于减缓HAE中MeV感染中心的增长,但它不是限制细胞间传播的主要因素.
- 独立于IFN的过程对于限制MeV在HAE中的细胞间传播至关重要.
- 由于MeV能够在空气道细胞中有效传播,而IFN诱导最小,这可能有助于MeV的高度传染性.
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