Pioneer transcription factors, progesterone receptor and Krüppel like transcription factor 4, cooperatively stimulate the bovine herpesvirus 1 ICP0 early promoter and productive late protein expression.

Pioneer transcription factors, progesterone receptor and Krüppel like transcription factor 4, cooperatively stimulate the bovine herpesvirus 1 ICP0 early promoter and productive late protein expression.
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DOI:
10.1016/j.virusres.2020.198115
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发表时间:
2020-10-15
期刊:
影响因子:
5
通讯作者:
Jones, Clinton
Jones, Clinton
中科院分区:
医学3区
文献类型:
--
作者:
Sawant, Laximan;Wijesekera, Nishani;Jones, Clinton

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牛疱疹病毒1型(BoHV-1),包括市售的改良活疫苗,很容易感染胎儿和卵巢,可导致生殖衰竭。感觉神经元中的BoHV-1潜伏-再激活周期进一步使生殖失败复杂化,因为孕酮偶尔诱导潜伏的再激活。孕酮受体(PR)和Krüppel样转录因子15(KLF 15)协同刺激生产性感染和立即早期转录单位1(IEtu 1)启动子。除了IEtu 1启动子外,bICP 0基因还含有一个单独的早期(E)启动子。在这项研究中,我们测试的假设,PR和KLF家族成员反式激活bICP 0 E启动子。PR和KLF 4以协同方式刺激bICP 0 E启动子活性和晚期生产性病毒蛋白表达。进一步的研究表明,bICP 0 E启动子内的三个增强子结构域对PR和KLF 4有反应。染色质免疫沉淀研究表明PR和KLF 4占据bICP 0 E启动子序列在转染的Neuro-2A细胞和牛肾细胞感染后的晚期。免疫共沉淀研究表明PR和KLF 4稳定地相互作用。这些研究表明PR和KLF 4协同激活bICP 0 E启动子与这些先驱转录因子之间的相互作用有关。
Bovine herpesvirus 1 (BoHV-1), including commercially available modified live vaccines, readily infect the fetus and ovaries, which can cause reproductive failure. The BoHV-1 latency-reactivation cycle in sensory neurons further complicates reproductive failure because progesterone sporadically induces reactivation from latency. The progesterone receptor (PR) and Krüppel-like transcription factor 15 (KLF15) cooperatively stimulate productive infection and the immediate early transcription unit 1 (IEtu1) promoter. In addition to the IEtu1 promoter, the bICP0 gene also contains a separate early (E) promoter. In this study, we tested the hypothesis that PR and KLF family members transactivate the bICP0 E promoter. PR and KLF4 stimulated bICP0 E promoter activity and expression of late productive viral protein expression in a cooperative manner. Additional studies revealed three enhancer domains within the bICP0 E promoter were responsive to PR and KLF4. Chromatin immunoprecipitation studies demonstrated PR and KLF4 occupy bICP0 E promoter sequences in transfected Neuro-2A cells and at late times following infection of bovine kidney cells. Co-immunoprecipitation studies indicated PR and KLF4 stably interact with each other. These studies suggest cooperative activation of the bICP0 E promoter by PR and KLF4 correlate with interactions between these pioneer transcription factors.
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