Source: School of Life Sciences
Written by: School of Life Sciences
Edited by: Tan Rongyu, Wang Dongmei

Recently, Prof. Jun Cui’s team from School of Life Sciences at Sun Yat-sen University published a research paper, entitled “Selective autophagy controls the stability of transcription factor IRF3 to balance type I interferon production and immune suppression”, in Autophagy (IF-5y = 11.966). In this study, researchers show that selective autophagy can target IRF3, the central transcriptional factor of IFN pathway, and balance the antiviral immune responses and immune suppression. This finding provides additional evidence to support the close correlation and provides novel molecular evidence on the dynamic modification of antiviral signaling network.

Interferon regulatory factor 3 (IRF3) is one of the most critical transcription factors in antiviral innate immune signaling. During viral infection, IRF3 modulates multiple cellular processes, including the initiation of type I IFN antiviral response as well as RLR-induced IRF3-mediated pathway of apoptosis. In recent decades, extensive studies have focused on the mechanisms underlying the post-translation modification, especially phosphorylation-triggered activation of IRF3. However, the mechanisms underlying the precise regulation of IRF3 activity are still not completely understood.

In this study, the researchers show that in latent state, deubiquitinase PSMD14 decreases the K27-linked ubiquitination of IRF3 at K313 to suppress its degradation, which subsequently maintains the basal level of IRF3 to ensure the activation of type I IFN signaling. Upon virus infection, PSMD14 disassociates with IRF3, and IRF3 then can be conjugated with K27-linked ubiquitin chains and goes through autophagic degradation in an NDP52-dependent manner, which leads to immune suppression. PSMD14 modulates the dynamic modification of IRF3 and controls the autophagic degradation of IRF3, thus balancing type I interferon production and immune suppression. This study not only reveals the dynamic modification and control of IRF3 during viral infection, but also provides further evidence to demonstrate the crosstalk between antiviral immune responses and selective autophagy.

Dr. Yaoxing Wu from School of Life Sciences of SYSU is the first author. Prof. Jun Cui is the corresponding author. This research is supported by the National Natural Science Foundation of China.

Link to the paper: https://www.tandfonline.com/doi/full/10.1080/15548627.2020.1761653