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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 PLoS+Pathog 2020 ; 16 (3): e1008429 Nephropedia Template TP
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BRD4 inhibition exerts anti-viral activity through DNA damage-dependent innate immune responses #MMPMID32208449
Wang J; Li GL; Ming SL; Wang CF; Shi LJ; Su BQ; Wu HT; Zeng L; Han YQ; Liu ZH; Jiang DW; Du YK; Li XD; Zhang GP; Yang GY; Chu BB
PLoS Pathog 2020[Mar]; 16 (3): e1008429 PMID32208449show ga
Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases.