Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production.
Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production.
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DOI：
10.3390/ijms23179799
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发表时间：
2022-08-29
影响因子：
5.6
通讯作者：
Nakamura, Hiroyuki
中科院分区：
文献类型：
--
作者：
Sakuragi, Sayuri;Liao, Huanan;Yajima, Kodai;Fujiwara, Shigeyoshi;Nakamura, Hiroyuki
关键词：
I型干扰素（IFN）应答是抵抗各种病原体的主要防御系统之一。虽然已知风疹病毒（RuV）感染会导致包括中枢神经系统在内的各种器官和系统的功能障碍，但对人类神经细胞如何引起针对RuV感染的保护性免疫，从而控制RuV复制知之甚少。利用培养的人神经细胞实验感染RuV RA 27/3株，我们的特点是对病毒的I型IFN免疫反应。RuV感染培养的人神经细胞系并诱导IFN-β的产生，导致信号转导和转录激活因子1（STAT 1）的激活以及IFN刺激基因（ISGs）的表达增加。黑色素瘤分化相关基因5（Melanoma-differentiation-associated gene 5，MDA 5）是RuV诱导的U373 MG细胞IFN-β mRNA表达所必需的细胞质视黄酸诱导基因I（retinoicacid-inducible gene I，RIG-I）样受体。我们还发现，通过使用IFNAR 2特异性中和抗体阻断IFN-α/β受体亚基2（IFNAR 2）或通过使用MAVS靶向短发夹RNA（shRNA）抑制线粒体抗病毒信号蛋白（MAVS）表达，RuV触发的ISG上调减弱。此外，用BX-795（一种TANK结合激酶1（TBK 1）/I κ B激酶ε（IKKε）抑制剂）处理RuV感染的细胞，稳健地降低了STAT 1磷酸化和ISG的表达，增强了病毒基因表达和感染性病毒体产生。总体而言，我们的研究结果表明，RuV触发的I型IFN介导的抗病毒反应是必不可少的控制RuV基因表达和病毒复制在人类神经细胞。
The type I interferon (IFN) response is one of the primary defense systems against various pathogens. Although rubella virus (RuV) infection is known to cause dysfunction of various organs and systems, including the central nervous system, little is known about how human neural cells evoke protective immunity against RuV infection, leading to controlling RuV replication. Using cultured human neural cells experimentally infected with RuV RA27/3 strain, we characterized the type I IFN immune response against the virus. RuV infected cultured human neural cell lines and induced IFN-β production, leading to the activation of signal transducer and activator of transcription 1 (STAT1) and the increased expression of IFN-stimulated genes (ISGs). Melanoma-differentiation-associated gene 5 (MDA5), one of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors, is required for the RuV-triggered IFN-β mRNA induction in U373MG cells. We also showed that upregulation of RuV-triggered ISGs was attenuated by blocking IFN-α/β receptor subunit 2 (IFNAR2) using an IFNAR2-specific neutralizing antibody or by repressing mitochondrial antiviral signaling protein (MAVS) expression using MAVS-targeting short hairpin RNA (shRNA). Furthermore, treating RuV-infected cells with BX-795, a TANK-binding kinase 1 (TBK1)/I kappa B kinase ε (IKKε) inhibitor, robustly reduced STAT1 phosphorylation and expression of ISGs, enhancing viral gene expression and infectious virion production. Overall, our findings suggest that the RuV-triggered type I IFN-mediated antiviral response is essential in controlling RuV gene expression and viral replication in human neural cells.
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影响因子：
3.8
作者：
CREMER, NE;OSHIRO, LS;CARNAY, L
通讯作者：
CARNAY, L
RIG-I 样受体的免疫信号传导。
影响因子：
32.4
作者：
Loo YM;Gale M Jr
通讯作者：
Gale M Jr
影响因子：
6.7
作者：
George, Suji;Viswanathan, Rajlakshmi;Sapkal, Gajanan N.
通讯作者：
Sapkal, Gajanan N.
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
影响因子：
14.5
作者：
CONNOLLY, JH;HUTCHINSON, WM;THOMSON, D
通讯作者：
THOMSON, D