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EB 病毒感染中 SUMO 修饰蛋白的变化鉴定了 TRIM24/28/33 复合物和裂解开关 BZLF1 的相互调节。

Changes in SUMO-modified proteins in Epstein-Barr virus infection identifies reciprocal regulation of TRIM24/28/33 complexes and the lytic switch BZLF1.

机构信息

Department of Molecular Genetics, University of Toronto, Toronto, Canada.

Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.

出版信息

PLoS Pathog. 2023 Jul 6;19(7):e1011477. doi: 10.1371/journal.ppat.1011477. eCollection 2023 Jul.

DOI:10.1371/journal.ppat.1011477
PMID:37410772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10353822/
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.

摘要

SUMO 修饰调节许多蛋白质的功能，在控制疱疹病毒感染中很重要。我们对 Epstein-Barr 病毒 (EBV) 潜伏和裂解感染中的 SUMO1 和 SUMO2 修饰蛋白进行了特异性蛋白质组分析，以鉴定响应 EBV 再激活而 SUMO 修饰状态发生变化的蛋白。在 TRIM24/TRIM28/TRIM33 复合物的所有三个成分中都发现了主要变化，TRIM24 迅速降解，TRIM33 在 EBV 裂解感染时发生磷酸化和 SUMO 化。进一步的实验表明，TRIM24 和 TRIM33 抑制 EBV BZLF1 裂解开关基因的表达，从而抑制 EBV 再激活。然而，BZLF1 被证明与 TRIM24 和 TRIM33 相互作用，导致 TRIM24/TRIM28/TRIM33 复合物解体，TRIM24 降解，TRIM33 修饰后降解。因此，我们确定了 TRIM24 和 TRIM33 是针对 EBV 裂解感染的细胞抗病毒防御因子，并建立了 BZLF1 使这种防御失效的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/bb0b3e8c1cdd/ppat.1011477.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/a22669411d08/ppat.1011477.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/3133126a3a3e/ppat.1011477.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/06c468e3173d/ppat.1011477.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/4fada46b19bf/ppat.1011477.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/dc44c6ae8997/ppat.1011477.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/e14794832593/ppat.1011477.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/e30b01c54a8e/ppat.1011477.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/999e9dacab6f/ppat.1011477.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/1cba2390f495/ppat.1011477.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/bb0b3e8c1cdd/ppat.1011477.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/a22669411d08/ppat.1011477.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/3133126a3a3e/ppat.1011477.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/06c468e3173d/ppat.1011477.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/4fada46b19bf/ppat.1011477.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/dc44c6ae8997/ppat.1011477.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/e14794832593/ppat.1011477.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/e30b01c54a8e/ppat.1011477.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/999e9dacab6f/ppat.1011477.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/1cba2390f495/ppat.1011477.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/10353822/bb0b3e8c1cdd/ppat.1011477.g010.jpg

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