PIM1 Attenuates Innate Immunity to Foster Coronavirus Replication through Ubiquitin Ligase β‐TrCP‐Mediated IFNAR1 Degradation

Qianya Wan; Lin Zhu; Cien Chen; Li Zhong; Houying Leung; Wei Li; Chang Xu; Xi Yao; Huan Hu; Mandi Wu; Yuxin Hou; Hin Chu; Yiran Wang; Sheng Chen; Mingyu Pan; Zongwei Cai; Ming‐liang He

doi:10.1002/advs.202503487

journal article·2025-10Open access

PIM1 Attenuates Innate Immunity to Foster Coronavirus Replication through Ubiquitin Ligase β‐TrCP‐Mediated IFNAR1 Degradation

Qianya Wan, Lin Zhu, Cien Chen, Li Zhong, Houying Leung, Wei Li, Chang Xu, Xi Yao, Huan Hu, Mandi Wu, Yuxin Hou, Hin Chu, Yiran Wang, Sheng Chen, Mingyu Pan, Zongwei Cai, Ming‐liang He

Advanced Science· Volume 12· Issue 37

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Source abstract

Abstract

Abstract Virus infection stimulates proto‐oncoprotein PIM1 kinase expression, but its importance and the biological functions of this process are poorly understood. Herein, PIM1 promotes IFNAR1 degradation to attenuate cellular innate immunity during human coronavirus HCoV‐OC43 infection. During virus replication, the double‐stranded viral RNA and some viral proteins upregulate PIM1 expression, which phosphorylates E3 ubiquitin ligase β‐TrCP1 at Serine 82. The pS82‐β‐TrCP1 then forms a complex with S535/S539‐phosphorylated interferon receptor IFNAR1 (pS535/539‐IFNAR1), leading to IFNAR1 ubiquitination and degradation. Both pan‐inhibitors (CX‐6528, SGI‐1776, AZD‐1208) and a specific inhibitor of PIM1 kinase (PIM1 inhibitor 2) effectively block this process and potently inhibit viral replication. This studies demonstrate a novel strategy that viruses use to disrupt cellular innate immunity, suggesting a potential therapeutic target for further anti‐virus drug development.

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Research context

OpenAlex topics: Cancer Mechanisms and Therapy · Phagocytosis and Immune Regulation · Peptidase Inhibition and Analysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Biomedical Sciences and Tung Biomedical Sciences Center City University of Hong Kong Hong Kong 999077 China

State Key Laboratory of Environmental and Biological Analysis Department of Chemistry, Hong Kong Baptist University Hong Kong 999077 China

Weihai Municipal Hospital Cheeloo College of Medicine Shandong University Shandong 264200 China

College of Medical Laboratory Dalian Medical University Dalian Liaoning 116044 China

State Key Laboratory of Emerging Infectious Diseases Department of Microbiology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong 999077 China

School of Pharmacy Nanjing Medical University Nanjing 211166 China

CityU Shenzhen Research Institute Nanshan Shenzhen 518057 China

Funding

City University of Hong Kong · Hong Kong Baptist University

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