BRD4 inhibition exerts anti-viral activity through DNA damage-dependent innate immune responses

• DOI: 10.1371/journal.ppat.1008429
• Publication Date: 2020-03-24T17:37:43Z
• Authors: Jiang Wang; Guo-Li Li; Sheng-Li Ming; Chun-Feng Wang; Li-Juan Shi; Bing-Qian Su; Hong-Tao Wu; Lei Zeng; Ying-Qian Han; Zhong-Hu Liu; Da-Wei Jiang; Yong-Kun Du; Xiang-Dong Li; Gai-Ping Zhang; Guo-Yu Yang; Bei-Bei Chu
• Keywords: Pseudorabies; BRD4

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various mechanisms have been identified the pathogenesis of human diseases. Here, we examined effects ten agents on pseudorabies virus (PRV) infection using GFP-reporter assays. Inhibitors bromodomain protein 4 (BRD4), which receives much more attention cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well a range DNA RNA viruses. We further demonstrated that BRD4 inhibition boosted robust innate immune response. also de-compacted chromatin structure induced damage response, thereby triggering activation cGAS-mediated immunity increasing host resistance both vitro vivo. Mechanistically, inhibitory effect mainly attributed attenuation attachment. Our findings reveal unique mechanism through restrains points its potent therapeutic value for infectious