DeSUMOylation of Apoptosis Inhibitor 5 by VP3 Supports Virus Replication

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2021 Aug 10

PMID 34372697

Citations 5

Authors

Tingjuan Deng

Boli Hu

Xingbo Wang

Yan Yan

Jianwei Zhou

Lulu Lin

Yuting Xu

Xiaojuan Zheng

Jiyong Zhou

Affiliations

Soon will be listed here.

Abstract

SUMOylation is a reversible posttranslational modification involved in the regulation of diverse biological processes. Growing evidence suggests that virus infection can interfere with the SUMOylation system. In the present study, we discovered that apoptosis inhibitor 5 (API5) is a SUMOylated protein. Amino acid substitution further identified that Lys404 of API5 was the critical residue for SUMO3 conjugation. Moreover, we found that infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. In addition, our results further revealed that viral protein VP3 inhibited the SUMOylation of API5 by targeting API5 and promoting UBC9 proteasome-dependent degradation through binding to the ubiquitin E3 ligase TRAF3. Furthermore, we revealed that wild-type but not K404R mutant API5 inhibited IBDV replication by enhancing MDA5-dependent IFN-β production. Taken together, our data demonstrate that API5 is a UBC9-dependent SUMOylated protein and deSUMOylation of API5 by viral protein VP3 aids in viral replication. Apoptosis inhibitor 5 (API5) is a nuclear protein initially identified for its antiapoptotic function. However, so far, posttranslational modification of API5 is unclear. In this study, we first identified that API5 K404 can be conjugated by SUMO3, and infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. Mechanically, viral protein VP3 directly interacts with API5 and inhibits SUMOylation of API5. Additionally, the cellular E3 ligase TNF receptor-associated factor 3 (TRAF3) is employed by VP3 to facilitate UBC9 proteasome-dependent degradation, leading to the reduction of API5 SUMOylation. Moreover, our data reveal that SUMOylation of API5 K404 promotes MDA5-dependent beta interferon (IFN-β) induction, and its deSUMOylation contributes to IBDV replication. This work highlights a critical role of conversion between SUMOylation and deSUMOylation of API5 in regulating viral replication.

Citing Articles

Apoptosis Inhibitor 5: A Multifaceted Regulator of Cell Fate.

Abbas H, Derkaoui D, Jeammet L, Adiceam E, Tiollier J, Sicard H Biomolecules. 2024; 14(1).

PMID: 38275765 PMC: 10813780. DOI: 10.3390/biom14010136.

The Formation and Function of Virus Factories.

Brodrick A, Broadbent A Int J Mol Sci. 2023; 24(10).

PMID: 37239817 PMC: 10218678. DOI: 10.3390/ijms24108471.

Interaction between chicken TRIM25 and MDA5 and their role in mediated antiviral activity against IBDV infection.

Diaz-Beneitez E, Cubas-Gaona L, Candelas-Rivera O, Benito-Zafra A, Sanchez-Aparicio M, Miorin L Front Microbiol. 2022; 13:1068328.

PMID: 36519174 PMC: 9742432. DOI: 10.3389/fmicb.2022.1068328.

Host Combats IBDV Infection at Both Protein and RNA Levels.

Zhang S, Zheng S Viruses. 2022; 14(10).

PMID: 36298864 PMC: 9607458. DOI: 10.3390/v14102309.

TRAF6 autophagic degradation by VP3 inhibits antiviral innate immunity via blocking NFKB/NF-κB activation.

Deng T, Hu B, Wang X, Ding S, Lin L, Yan Y Autophagy. 2022; 18(12):2781-2798.

PMID: 35266845 PMC: 9673932. DOI: 10.1080/15548627.2022.2047384.

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