I型干扰素通路负调节因子的筛选和验证。

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Zhaojun Pang, Han Yang, Bo Li, Yifu Liu, Zhenxiang Zhao, Zixiang Zhu, Shouchun Peng, Xin Mu, Hongjian Yu
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引用次数: 0

摘要

I型干扰素(IFN-I)是抗病毒反应和免疫调节的关键蛋白。负调节因子通过多种机制避免干扰素通路的异常激活或干扰素激活蛋白的过度激活。负调节基因的功能丧失突变导致各种I型干扰素病的发展。发现新的负调节因子并研究其功能具有重要的理论和临床意义,但目前尚无有效的筛选系统。本研究通过抗性报告基因建立筛选系统,该基因仅在干扰素通路激活的细胞中表达。结合CRISPR敲除文库,筛选因敲除负调节因子而激活干扰素通路的细胞,从而鉴定出负调节因子候选基因,如PCGF3/5、UCK2和ITPKA。这些基因的表达产物以MAVS为靶点,通过抑制干扰素通路激活促进EMCV(脑心肌炎病毒)感染。本研究加深了对干扰素通路调控网络的认识,为自身免疫性疾病发病机制的研究提供了新的理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Screening and Validation of Negative Regulators of the Type I Interferon Pathway.

Type I interferons (IFN-I) are key proteins in antiviral response and immunomodulation. Negative regulators avoid abnormal activation of the interferon pathway or overactivation of interferon-activating proteins through multiple mechanisms. Loss-of-function mutations in negative regulator genes lead to the development of a variety of type I interferonopathy. It is of great significance in theory and clinic to discover new negative regulators and study their functions, but there is no effective screening system at present. Here, a screening system is established through a resistance reporter, which is designed to be expressed only in cells with interferon pathway activation. In conjunction with CRISPR knockout library, cells are screened for interferon pathway activation due to knockout of negatively regulators, which led to the identification of negatively regulator candidate genes such as PCGF3/5, UCK2, and ITPKA. The expression products of these genes functioned by targeting MAVS and promoted EMCV (encephalomyocarditis virus) infection by inhibiting interferon pathway activation. This study deepens the understanding of the regulatory network of the interferon pathway and provides a new theoretical basis for the study of the pathogenesis of autoimmune diseases.

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来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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