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An Epigenetic Compound Library Screen Identifies BET Inhibitors That Promote HSV-1 and -2 Replication by Bridging P-TEFb to Viral Gene Promoters through BRD4
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نویسنده
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ren k. ,zhang w. ,chen x. ,ma y. ,dai y. ,fan y. ,hou y. ,tan r.x. ,li e.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 10
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چکیده
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The human hsv-1 and -2 are common pathogens of human diseases. both host and viral factors are involved in hsv lytic infection,although detailed mechanisms remain elusive. by screening a chemical library of epigenetic regulation,we identified bromodomain-containing protein 4 (brd4) as a critical player in hsv infection. we show that treatment with pan bd domain inhibitor enhanced both hsv infection. using jq1 as a probe,we found that jq1,a defined bd1 inhibitor,acts through brd4 protein since knockdown of brd4 expression ablated jq1 effect on hsv infection. brd4 regulates hsv replication through complex formation involving cdk9 and rnap ii; whereas,jq1 promotes hsv-1 infection by allocating the complex to hsv gene promoters. therefore,suppression of brd4 expression or inhibition of cdk9 activity impeded hsv infection. our data support a model that jq1 enhances hsv infection by switching brd4 to transcription regulation of viral gene expression from chromatin targeting since transient expression of brd4 bd1 or bd1/2 domain had similar effect to that by jq1 treatment. in addition to the identification that brd4 is a modulator for jq1 action on hsv infection,this study demonstrates brd4 has an essential role in hsv infection. © 2016 ren et al.
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آدرس
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medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing,china,jiangsu laboratory of molecular medicine,medical school,nanjing university,nanjing, China, medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing,china,jiangsu laboratory of molecular medicine,medical school,nanjing university,nanjing, China, the hoffmann institute of immunology,guangzhou medical university,guangzhou, China, medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing,china,jiangsu laboratory of molecular medicine,medical school,nanjing university,nanjing, China, jiangsu laboratory of molecular medicine,medical school,nanjing university,nanjing, China, medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing, China, medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing, China, medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing,china,jiangsu laboratory of molecular medicine,medical school,nanjing university,nanjing,china,nanjing university of chinese medicine,nanjing, China, medical school and state key laboratory of pharmaceutical biotechnology,nanjing university,nanjing,china,jiangsu laboratory of molecular medicine,medical school,nanjing university,nanjing, China
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Authors
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