Histone positioning and modifications on viral genomes are important factors regulating virus replication. To investigate the dynamics of modified histones on the viral genome and their potential roles in antiviral response, we studied the dynamic changes of histone modifications across the HSV-1 genome in THP-1 cells. Histone modifications were detected on the HSV-1 genome soon after infection, including H3K9me3, H3K27me3, H3K4me3 and H3K27ac. These modifications emerged on the viral genome soon after infection and changed rapidly along with virus life cycle progression. The transcription repression marks, H3K9me3 and H3K27me3, decreased on the viral genome during the infection process; the transcription activation mark H3K27ac increased. Treatment with C646, an inhibitor of H3K27ac transferase p300, significantly repressed virus replication and viral gene expression. Our study reveals the relationship between histone modifications and viral gene expression and provides potential novel strategies for antiviral treatment.

中文翻译：

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人THP-1细胞中HSV-1基因组的组蛋白修饰的表观遗传学景观。

组蛋白在病毒基因组上的定位和修饰是调节病毒复制的重要因素。为了研究病毒基因组上修饰的组蛋白的动力学及其在抗病毒应答中的潜在作用，我们研究了THP-1细胞中HSV-1基因组中组蛋白修饰的动态变化。感染后不久在HSV-1基因组上检测到组蛋白修饰，包括H3K9me3，H3K27me3，H3K4me3和H3K27ac。这些修饰在感染后不久就出现在病毒基因组上，并且随着病毒生命周期的发展而迅速改变。在感染过程中，病毒基因组上的转录阻抑标记H3K9me3和H3K27me3减少了。转录激活标记H3K27ac增加。用H3K27ac转移酶p300抑制剂C646治疗，显着抑制病毒复制和病毒基因表达。我们的研究揭示了组蛋白修饰和病毒基因表达之间的关系，并提供了抗病毒治疗的潜在新策略。