RNF5: inhibiting antiviral immunity and shaping virus life cycle

Junyi Ge; Leiliang Zhang

doi:10.3389/fimmu.2023.1324516

RNF5: inhibiting antiviral immunity and shaping virus life cycle

Front Immunol. 2024 Jan 5:14:1324516. doi: 10.3389/fimmu.2023.1324516. eCollection 2023.

Authors

Junyi Ge^{1

2

3}, Leiliang Zhang^{1

2

3}

Affiliations

¹ Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
² Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
³ Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Abstract

RNF5 is an E3 ubiquitin ligase involved in various physiological processes such as protein localization and cancer progression. Recent studies have shown that RNF5 significantly inhibits antiviral innate immunity by promoting the ubiquitination and degradation of STING and MAVS, which are essential adaptor proteins, as well as their downstream signal IRF3. The abundance of RNF5 is delicately regulated by both host factors and viruses. Host factors have been found to restrict RNF5-mediated ubiquitination, maintaining the stability of STING or MAVS through distinct mechanisms. Meanwhile, viruses have developed ingenious strategies to hijack RNF5 to ubiquitinate and degrade immune proteins. Moreover, recent studies have revealed the multifaceted roles of RNF5 in the life cycle of various viruses, including SARS-CoV-2 and KSHV. Based on these emerging discoveries, RNF5 represents a novel means of modulating antiviral immunity. In this review, we summarize the latest research on the roles of RNF5 in antiviral immunity and virus life cycle. This comprehensive understanding could offer valuable insights into exploring potential therapeutic applications focused on targeting RNF5 during viral infections.

Keywords: IRF3; MAVS; RNF5; SARS-CoV-2; STING.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing*
Immunity, Innate*
Protein Transport
Ubiquitin-Protein Ligases* / immunology
Virus Diseases* / immunology

Substances

Adaptor Proteins, Signal Transducing
Ubiquitin-Protein Ligases

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (82272306 and 82072270); Taishan Scholars Program (tstp20221142); and Academic Promotion Program of Shandong First Medical University (2019LJ001).