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    Home > Active Ingredient News > Immunology News > PLOS Pathog: Henan Agricultural Da Baibe/Yang Guoyu and other analysis of BRD4 in the anti-viral natural immunity of the important function.

    PLOS Pathog: Henan Agricultural Da Baibe/Yang Guoyu and other analysis of BRD4 in the anti-viral natural immunity of the important function.

    • Last Update: 2020-07-22
    • Source: Internet
    • Author: User
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    Chromatin epigenetic modification plays an important role in maintaining chromatin homeostasis and gene expression.these modifications mainly include DNA methylation / demethylation modification, histone acetylation / deacetylation modification and histone methylation / demethylation modification.abnormal regulation of chromatin epigenetic modification is closely related to the occurrence of many diseases.the bromine domain and extra terminal domain (BET) contains four proteins, namely BRD2, BRD3, Brd4 and BRDT.among them, Brd4 protein is the most important functional protein in bet family, which contains two bromine domains and one super terminal domain.Brd4 binds acetylated histones through its bromine domain, thus recruiting different transcription factors to regulate the expression of target genes.in addition, Brd4 itself has histone acetyltransferase activity.previous studies on Brd4 and virus replication have shown that Brd4 is closely related to viral gene transcription.however, there is no report on Brd4 and antiviral innate immunity.on March 25, Chu Beibei and Yang Guoyu, School of animal husbandry and medical engineering, Henan Agricultural University, published a research paper entitled: Brd4 investment exerts anti virtual activity through DNA damage dependent intrinsic immune responses on PLoS pathogens.the important functions of Brd4 in antiviral innate immunity were analyzed in detail.in order to explore the important function of chromatin epigenetic modification in the process of virus replication, we screened 10 inhibitors of chromatin epigenetic modification by using the recombinant prv-gfp reporter gene system of pseudorabies virus.it was found that three Brd4 inhibitors JQ-1, otx-015 and i-bet 151 could significantly inhibit prv-gfp replication.further studies showed that both Brd4 inhibitors and RNA interference could inhibit PRV, herpes simplex virus 1 (HSV1), ectomelia virus (ECTV), vascular stomatitis virus (VSV), porcine reproductive and respiratory syndrome virus (PRRSV), Newcastle disease virus (NDV) and influenza virus (H1N1).inhibition of Brd4 does not affect the transcription of PRV UL9, UL5, US1 and PRRSV ORF7 genes, but inhibits the adsorption stage between the virus and host cells, thus inhibiting virus replication.the authors further found that inhibition of Brd4 can activate interferon regulated factor 3 (IRF3) - dependent antiviral innate immunity.this is mainly due to the loose chromatin structure caused by inhibition of Brd4, resulting in DNA damage (DDR), and finally activating antiviral innate immunity through DDR dependent CGAs / sting innate immune signal pathway. in addition, the Brd4 inhibitor JQ-1 had good inhibitory effect on PRV and H1N1 in mice. the highlight of this work is the first time to reveal the inhibition of Brd4 to activate antiviral innate immunity through DNA damage dependent CGAs / sting / tbk1 / IRF3 pathway. in addition, this study also provides reference value for Brd4 inhibitors in sting based tumor immunotherapy. Chu Beibei has been selected as the top-notch young talents of the ten thousand talents program of the Organization Department of the CPC Central Committee, the high-level talents of Henan Province, the academic and technological leaders of Henan Province and the young backbone teachers of Henan Province. the research direction of the research group mainly focuses on the interaction between virus and host. postdoctoral students, doctoral students and master students related to biochemistry, molecular biology, cell biology and immunology are welcome to contact us via email (chubeibei)_ hau@hotmail.com )Paper links:
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