Viperin weakens IFN-I-induced immune activity by facilitating STAT1 degradation through E3 ligase UBE4A

Viperin is considered as an antiviral protein known to directly target a variety of viruses. However, whether and how Viperin affects virus infection by targeting intracellular immune signaling remain unexplored. Here, we reveal that Viperin inhibits type-I interferon (IFN-I) antiviral immune signaling by degrading STAT1. We found that IFN-I upregulates the ubiquitin E3 ligase ITCH to degrade UBR5, while Viperin subsequently recruits another ubiquitin E3 ligase UBE4A to promote STAT1 ubiquitination and degradation to attenuate IFN-I signaling. Moreover, the multifunctional interfering peptide VS-IP1 can block Viperin-mediated STAT1 degradation, thus enhancing IFN-I antiviral immune function. This study reveals that Viperin is a suppressor of IFN-I immune signaling, which could renew understanding of the biological function of Viperin, and provide a strategy for enhancing clinical IFN-I therapeutic efficacy.

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Publication Details

Journal
Cell Insight
Published
2026-04-03
DOI
https://doi.org/10.1016/j.cellin.2026.100322
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
0.00

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article

Viperin weakens IFN-I-induced immune activity by facilitating STAT1 degradation through E3 ligase UBE4A

Qi Cui, Liping Qian, Renxia Zhang, Yanou Li et al.
Cell Insight
interferon and immune responses
article

Viperin weakens IFN-I-induced immune activity by facilitating STAT1 degradation through E3 ligase UBE4A

Qi Cui, Liping Qian, Renxia Zhang, Yanou Li, Zhize Li, Yong Yu, Hui Zheng, Tingting Zhang, Yukang Yuan, Qian Zhao, Jun Wang, Sidong Xiong, Ying Miao
article en

Abstract

Viperin is considered as an antiviral protein known to directly target a variety of viruses. However, whether and how Viperin affects virus infection by targeting intracellular immune signaling remain unexplored. Here, we reveal that Viperin inhibits type-I interferon (IFN-I) antiviral immune signaling by degrading STAT1. We found that IFN-I upregulates the ubiquitin E3 ligase ITCH to degrade UBR5, while Viperin subsequently recruits another ubiquitin E3 ligase UBE4A to promote STAT1 ubiquitination and degradation to attenuate IFN-I signaling. Moreover, the multifunctional interfering peptide VS-IP1 can block Viperin-mediated STAT1 degradation, thus enhancing IFN-I antiviral immune function. This study reveals that Viperin is a suppressor of IFN-I immune signaling, which could renew understanding of the biological function of Viperin, and provide a strategy for enhancing clinical IFN-I therapeutic efficacy.

Cell InsightVol. 5(3)
University of Electronic Science and Technology of China (CN), Sun Yat-sen University (CN), Sichuan University (CN), Fudan University (CN), Soochow University (CN), Second Affiliated Hospital of Soochow University (CN), Zhongshan Hospital (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), First Affiliated Hospital of Soochow University (CN), Institute of Infection and Immunity (CA)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, Priority Academic Program Development of Jiangsu Higher Education Institutions, Sichuan Province Science and Technology Support Program, National Key Research and Development Program of China, National Key Research and Development Program of China Stem Cell and Translational Research
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interferon and immune responses
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