UBL7 enhances antiviral innate immunity by promoting Lys27-linked polyubiquitination of MAVS

Wei Jiang; Xinyu Li; Henan Xu; Xiuling Gu; Shan Li; Li Zhu; Jiao Lu; Xuefeng Duan; Wei Li; Min Fang

doi:10.1016/j.celrep.2023.112272

UBL7 enhances antiviral innate immunity by promoting Lys27-linked polyubiquitination of MAVS

Cell Rep. 2023 Mar 28;42(3):112272. doi: 10.1016/j.celrep.2023.112272. Epub 2023 Mar 20.

Authors

Wei Jiang¹, Xinyu Li², Henan Xu¹, Xiuling Gu², Shan Li², Li Zhu¹, Jiao Lu¹, Xuefeng Duan¹, Wei Li³, Min Fang⁴

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ Institute of Reproductive Health and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; International College, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: fangm@im.ac.cn.

PMID: 36943869
DOI: 10.1016/j.celrep.2023.112272

Abstract

RNA virus infection usually triggers a range of host immune responses, including the induction of proinflammatory cytokines, interferons, and interferon-stimulated genes (ISGs). Here, we report that UBL7, a ubiquitin-like protein, is upregulated during RNA virus infection and induced by type I interferon as an ISG. UBL7-deficient mice exhibit increased susceptibility to viral infection due to attenuated antiviral innate immunity. UBL7 enhances innate immune response to viral infection by promoting the K27-linked polyubiquitination of MAVS. UBL7 interacts with TRIM21, an E3 ubiquitin ligase of MAVS, and promotes the combination of TRIM21 with MAVS in a dose-dependent manner, facilitating the K27-linked polyubiquitination of MAVS and recruiting of TBK1 to enhance the IFN signaling pathway. Moreover, UBL7 has a broad-spectrum antiviral function as an immunomodulatory adaptor protein. Therefore, UBL7 positively regulates innate antiviral signaling and promotes positive feedback to enhance and amplify the antiviral response.

Keywords: CP: Immunology; Innate immunity; Interferon-stimulated genes; K27-linked polyubiquitination; MAVS; TRIM21; UBL7.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents
Immunity, Innate
Interferon Type I* / metabolism
Mice
RNA Virus Infections*
Ubiquitin / metabolism
Virus Diseases*

Substances

Antiviral Agents
Interferon Type I
Ubiquitin