beta-Catenin-Specific Inhibitor, iCRT14, Promotes BoHV-1 Infection-Induced DNA Damage in Human A549 Lung Adenocarcinoma Cells by Enhancing Viral Protein Expression

文献类型： 外文期刊

第一作者： Ding, Xiuyan

作者： Ding, Xiuyan;Yang, Hao;Liu, Chang;Zhu, Liqian;Ding, Xiuyan;Zhu, Liqian;Yuan, Weifeng;Li, Shitao;Zhu, Liqian

作者机构：

关键词： BoHV-1; beta-catenin; 53BP1; gamma H2AX; DNA damage

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：6.208； 五年影响因子：6.628 ）

ISSN：

年卷期： 2022 年 23 卷 4 期

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收录情况： SCI

摘要： Oncolytic bovine herpesvirus type 1 (BoHV-1) infection induces DNA damage in human lung adenocarcinoma cell line A549. However, the underlying mechanisms are not fully understood. We found that BoHV-1 infection decreased the steady-state protein levels of p53-binding protein 1 (53BP1), which plays a central role in dictating DNA damage repair and maintaining genomic stability. Furthermore, BoHV-1 impaired the formation of 53BP1 foci, suggesting that BoHV-1 inhibits 53BP1-mediated DNA damage repair. Interestingly, BoHV-1 infection redistributed intracellular beta-catenin, and iCRT14 (5-[[2,5-Dimethyl-1-(3-pyridinyl)-1H-pyrrol-3-yl]methylene]-3-phenyl-2,4-thiazolidinedione), a beta-catenin-specific inhibitor, enhanced certain viral protein expression, such as the envelope glycoproteins gC and gD, and enhanced virus infection-induced DNA damage. Therefore, for the first time, we provide evidence showing that BoHV-1 infection disrupts 53BP1-mediated DNA damage repair and suggest beta-catenin as a potential host factor restricting both virus replication and DNA damage in A549 cells.

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