Human papillomaviruses (HPV) are a large family of viruses which contain a circular, double-stranded DNA genome of approximately 8000 base pairs. The viral DNA is chromatinized by the recruitment of cellular histones which are subject to host cell–mediated post-translational epigenetic modification recognized as an important mechanism of virus transcription regulation. The HPV life cycle is dependent on the terminal differentiation of the target cell within epithelia—the keratinocyte. The virus life cycle begins in the undifferentiated basal compartment of epithelia where the viral chromatin is maintained in an epigenetically repressed state, stabilized by distal chromatin interactions between the viral enhancer and early gene region. Migration of the infected keratinocyte towards the surface of the epithelium induces cellular differentiation which disrupts chromatin looping and stimulates epigenetic remodelling of the viral chromatin. These epigenetic changes result in enhanced virus transcription and activation of the virus late promoter facilitating transcription of the viral capsid proteins. In this review article, we discuss the complexity of virus- and host-cell-mediated epigenetic regulation of virus transcription with a specific focus on differentiation-dependent remodelling of viral chromatin during the HPV life cycle.

中文翻译：

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人乳头瘤病毒在病毒生命周期中转录的表观遗传调控。

人乳头瘤病毒 (HPV) 是一个病毒大家族，包含约 8000 个碱基对的环状双链 DNA 基因组。病毒 DNA 通过招募细胞组蛋白进行染色质化，这些组蛋白受到宿主细胞介导的翻译后表观遗传修饰的影响，被认为是病毒转录调控的重要机制。HPV 生命周期取决于上皮内靶细胞（角质形成细胞）的终末分化。病毒生命周期开始于上皮细胞的未分化基底区室，其中病毒染色质维持在表观遗传抑制状态，并通过病毒增强子和早期基因区域之间的远端染色质相互作用来稳定。受感染的角质形成细胞向上皮表面迁移会诱导细胞分化，从而破坏染色质循环并刺激病毒染色质的表观遗传重塑。这些表观遗传变化导致病毒转录增强，并激活病毒晚期启动子，促进病毒衣壳蛋白的转录。在这篇综述文章中，我们讨论了病毒和宿主细胞介导的病毒转录表观遗传调控的复杂性，特别关注 HPV 生命周期中病毒染色质的分化依赖性重塑。