College of Life Science, Institute of Life Science and Green Development, Hebei University, Baoding 071002, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Int J Mol Sci. 2022 Feb 19;23(4):2328. doi: 10.3390/ijms23042328.
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 β-catenin, and iCRT14 (5-[[2,5-Dimethyl-1-(3-pyridinyl)-1H-pyrrol-3-yl]methylene]-3-phenyl-2,4-thiazolidinedione), a β-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 β-catenin as a potential host factor restricting both virus replication and DNA damage in A549 cells.
溶瘤牛疱疹病毒 1 型（BoHV-1）感染诱导人肺腺癌细胞系 A549 中的 DNA 损伤。然而，其潜在机制尚未完全阐明。我们发现 BoHV-1 感染降低了 p53 结合蛋白 1（53BP1）的稳定蛋白水平，而 53BP1 在决定 DNA 损伤修复和维持基因组稳定性方面起着核心作用。此外，BoHV-1 损害了 53BP1 焦点的形成，表明 BoHV-1 抑制 53BP1 介导的 DNA 损伤修复。有趣的是，BoHV-1 感染重新分配了细胞内 β-连环蛋白，并且 β-连环蛋白特异性抑制剂 iCRT14（5-[[2,5-二甲基-1-(3-吡啶基)-1H-吡咯-3-基]亚甲基]-3-苯基-2,4-噻唑烷二酮）增强了某些病毒蛋白的表达，如包膜糖蛋白 gC 和 gD，并增强了病毒感染诱导的 DNA 损伤。因此，我们首次提供证据表明 BoHV-1 感染破坏了 53BP1 介导的 DNA 损伤修复，并表明 β-连环蛋白作为一种潜在的宿主因子，限制了 A549 细胞中的病毒复制和 DNA 损伤。
