Deubiquitinase OTUD6A Regulates Innate Immune Response via Targeting UBC13

Zhiwei Li; Guanwen Li; Yunfei Li; Yujie Luo; Yuhan Jiang; Ziyu Zhang; Ziyi Zhou; Shengde Liu; Chen Wu; Fuping You

doi:10.3390/v15081761

Deubiquitinase OTUD6A Regulates Innate Immune Response via Targeting UBC13

Viruses. 2023 Aug 18;15(8):1761. doi: 10.3390/v15081761.

Authors

Zhiwei Li¹, Guanwen Li², Yunfei Li³, Yujie Luo³, Yuhan Jiang¹, Ziyu Zhang¹, Ziyi Zhou¹, Shengde Liu⁴, Chen Wu¹, Fuping You³

Affiliations

¹ College of Life Sciences, Hebei University, Baoding 071002, China.
² College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
³ Department of Systems Biomedicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
⁴ Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Abstract

OTUD6A is a deubiquitinase that plays crucial roles in various human diseases. However, the precise regulatory mechanism of OTUD6A remains unclear. In this study, we found that OTUD6A significantly inhibited the production of type I interferon. Consistently, peritoneal macrophages and bone marrow-derived macrophages from Otud6a-/- mice produced more type I interferon after virus infection compared to cells from WT mice. Otud6a-/-^- mice also exhibited increased resistance to lethal HSV-1 and VSV infections, as well as LPS attacks due to decreased inflammatory responses. Mechanistically, mass spectrometry results revealed that UBC13 was an OTUD6A-interacting protein, and the interaction was significantly enhanced after HSV-1 stimulation. Taken together, our findings suggest that OTUD6A plays a crucial role in the innate immune response and may serve as a potential therapeutic target for infectious disease.

Keywords: IFNβ; NF-κB; OTUD6A; UBC13; innate immunity.

Publication types

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

MeSH terms

Animals
Deubiquitinating Enzymes
Herpesvirus 1, Human*
Humans
Immunity, Innate
Interferon Type I*
Macrophages
Mice

Substances

Interferon Type I
Deubiquitinating Enzymes

Grants and funding

This work was supported by Beijing Natural Science Foundation (Z210014), the National Key Research and Development Program of China (SQ2021YFC2300055, 2021YFC2302602, 2020YFA0707800), The National Natural Science Foundation of China (82221003, 31570891; 31872736; 32022028; 81991505; 82201928), and Peking University Clinical + X (PKU2020LCXQ009).