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Screening and Validation of Negative Regulators of the Type I Interferon Pathway

文献类型： 外文期刊

作者： Pang, Zhaojun 1 ; Yang, Han 2 ; Li, Bo 3 ; Liu, Yifu 1 ; Zhao, Zhenxiang 4 ; Zhu, Zixiang 4 ; Peng, Shouchun 5 ; Mu, Xin 1 ; Yu, Hongjian 5 ;

作者机构： 1.Tianjin Univ, Tianjin Univ & Hlth Biotech United Grp Joint Lab I, Sch Pharmaceut Sci & Technol, Fac Med, Tianjin 300072, Peoples R China

2.Chinese Acad Med Sci, Inst Geriatr Med, Natl Ctr Gerontol, Beijing Hosp,Clin Trial Res Ctr, Beijing 100730, Peoples R China

3.Jinzhou Med Univ, Dept Pathol, Jinzhou 121001, Peoples R China

4.Lanzhou Univ, Chinese Acad Agr Sci, State Key Lab Anim Dis Control & Prevent, Lanzhou Vet Res Inst,Coll Vet Med, Lanzhou 730046, Peoples R China

5.Tianjin Univ, Jinnan Hosp, Tianjin Jinnan Hosp, Tianjin 300350, Peoples R China

6.Tianjin Univ, Acad Med Engn & Translat Med, Tianjin 300072, Peoples R China

关键词： CRISPR KO library; interferon, ITPKA; MAVS; negative regulators; PCGF3, UCK2

期刊名称：ADVANCED BIOLOGY （ 影响因子：2.6； 五年影响因子：3.2 ）

ISSN： 2701-0198

年卷期： 2025 年

页码：

收录情况： SCI

摘要： 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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[1]Screening and Validation of Negative Regulators of the Type I Interferon Pathway. Pang, Zhaojun,Liu, Yifu,Mu, Xin,Pang, Zhaojun,Liu, Yifu,Mu, Xin,Yang, Han,Li, Bo,Zhao, Zhenxiang,Zhu, Zixiang,Peng, Shouchun,Mu, Xin,Yu, Hongjian,Peng, Shouchun. 2025

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