Changes in SUMO-modified Proteins in Epstein-Barr Virus Infection Identifies Reciprocal Regulation of TRIM24/28/33 Complexes and the Lytic Switch BZLF1

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2023 Jul 6

PMID 37410772

Authors

Carlos F De La Cruz-Herrera

Michael H Tatham

Umama Z Siddiqi

Kathy Shire

Edyta Marcon

Jack F Greenblatt

Ronald T Hay

Lori Frappier

Affiliations

Soon will be listed here.

Abstract

SUMO modifications regulate the function of many proteins and are important in controlling herpesvirus infections. We performed a site-specific proteomic analysis of SUMO1- and SUMO2-modified proteins in Epstein-Barr virus (EBV) latent and lytic infection to identify proteins that change in SUMO modification status in response to EBV reactivation. Major changes were identified in all three components of the TRIM24/TRIM28/TRIM33 complex, with TRIM24 being rapidly degraded and TRIM33 being phosphorylated and SUMOylated in response to EBV lytic infection. Further experiments revealed TRIM24 and TRIM33 repress expression of the EBV BZLF1 lytic switch gene, suppressing EBV reactivation. However, BZLF1 was shown to interact with TRIM24 and TRIM33, resulting in disruption of TRIM24/TRIM28/TRIM33 complexes, degradation of TRIM24 and modification followed by degradation of TRIM33. Therefore, we have identified TRIM24 and TRIM33 as cellular antiviral defence factors against EBV lytic infection and established the mechanism by which BZLF1 disables this defence.

Citing Articles

Identifying the key regulators orchestrating Epstein-Barr virus reactivation.

Wang Y, Yu J, Pei Y Front Microbiol. 2024; 15:1505191.

PMID: 39703703 PMC: 11655498. DOI: 10.3389/fmicb.2024.1505191.

TRIM Proteins: Key Regulators of Immunity to Herpesvirus Infection.

Sayyad Z, Acharya D, Gack M Viruses. 2024; 16(11).

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