Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Deubiquitinase OTUD6A Regulates Innate Immune Response Via Targeting Ubc13

Version 1 : Received: 26 June 2023 / Approved: 27 June 2023 / Online: 27 June 2023 (11:42:11 CEST)

A peer-reviewed article of this Preprint also exists.

Li, Z.; Li, G.; Li, Y.; Luo, Y.; Jiang, Y.; Zhang, Z.; Zhou, Z.; Liu, S.; Wu, C.; You, F. Deubiquitinase OTUD6A Regulates Innate Immune Response via Targeting UBC13. Viruses 2023, 15, 1761. Li, Z.; Li, G.; Li, Y.; Luo, Y.; Jiang, Y.; Zhang, Z.; Zhou, Z.; Liu, S.; Wu, C.; You, F. Deubiquitinase OTUD6A Regulates Innate Immune Response via Targeting UBC13. Viruses 2023, 15, 1761.

Abstract

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 attack due to decreased inflammatory responses. Mechanistically, mass spectrometry results revealed that UBC13 was an OTUD6A-interacting protein, and the interaction 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

OTUD6A; IFNβ; Ubc13; NF-κB; innate immunity

Subject

Biology and Life Sciences, Immunology and Microbiology

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