Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy.
Chromatin-mediated epigenetic regulation of HSV-1 transcription as a potential target in antiviral therapy.
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DOI：
10.1016/j.antiviral.2021.105103
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发表时间：
2021-08
影响因子：
7.6
通讯作者：
Sun K
中科院分区：
文献类型：
--
作者：
Schang LM;Hu M;Cortes EF;Sun K
建立潜伏感染并从潜伏感染中重新激活的能力是HSV-1生物学和发病机制的核心。这也对抗病毒治疗提出了强大的挑战，因为潜伏的HSV-1基因组不复制或表达任何靶向蛋白。虽然调控潜伏期的建立和维持以及潜伏期的重新激活的过程还没有完全阐明，但目前的普遍共识是，表观遗传学发挥了主要作用。一个统一的模型假设，虽然HSV-1在溶血性感染中避免或抵消染色质沉默，但它在潜伏期变得沉默，沉默在重新激活过程中某种程度上被破坏。不同小组使用各种方法进行的多年工作也表明，裂解的HSV-1染色质是独特的，具有大多数细胞染色质所不具备的独特的生物物理性质。然而，裂解和潜伏的病毒染色质通常分别富含翻译后修饰或组蛋白变体，其特征是激活或抑制转录。此外，各种小分子表观遗传调节剂从潜伏期开始抑制病毒复制和重新激活。尽管在培养和动物模型中取得了这些成功，但如果同样的表观遗传机制控制病毒和细胞的基因表达，表观遗传调节将如何用于抗病毒治疗并不明显。最近的工作突出了病毒染色质和细胞染色质之间的几个重要差异，这些差异似乎与它们各自的表观遗传调控有关。在这篇综述中，我们将讨论病毒染色质的特殊性，并探索它是否受到足够独特的机制的调节，以用于抗病毒治疗。
The ability to establish, and reactivate from, latent infections is central to the biology and pathogenesis of HSV-1. It also poses a strong challenge to antiviral therapy, as latent HSV-1 genomes do not replicate or express any protein to be targeted. Although the processes regulating the establishment and maintenance of, and reactivation from, latency are not fully elucidated, the current general consensus is that epigenetics play a major role. A unifying model postulates that whereas HSV-1 avoids or counteracts chromatin silencing in lytic infections, it becomes silenced during latency, silencing which is somewhat disrupted during reactivation. Many years of work by different groups using a variety of approaches have also shown that the lytic HSV-1 chromatin is distinct and has unique biophysical properties not shared with most cellular chromatin. Nonetheless, the lytic and latent viral chromatins are typically enriched in post translational modifications or histone variants characteristic of active or repressed transcription, respectively. Moreover, a variety of small molecule epigenetic modulators inhibit viral replication and reactivation from latency. Despite these successes in culture and animal models, it is not obvious how epigenetic modulation would be used in antiviral therapy if the same epigenetic mechanisms governed viral and cellular gene expression. Recent work has highlighted several important differences between the viral and cellular chromatins, which appear to be of consequence to their respective epigenetic regulations. In this review, we will discuss the distinctiveness of the viral chromatin, and explore whether it is regulated by mechanisms unique enough to be exploited in antiviral therapy.
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