We are at an interesting time in the understanding of alpha herpesvirus latency and reactivation and their implications to human disease. Conceptual advances have come from both animal and neuronal culture models. This review focuses on the concept that the tegument protein and viral transactivator VP16 plays a major role in the transition from latency to the lytic cycle. During acute infection, regulation of VP16 transactivation balances spread in the nervous system, establishment of latent infections and virulence. Reactivation is dependent on this transactivator to drive entry into the lytic cycle. In vivo de novo expression of VP16 protein is mediated by sequences conferring pre-immediate early transcription embedded in the normally leaky late promoter. In vitro, alternate mechanisms regulating VP16 expression in the context of latency have come from the SCG neuron culture model and include the concepts that (i) generalized transcriptional derepression of the viral genome and sequestration of VP16 in the cytoplasm for ~48 hours (Phase I) precedes and is required for VP16-dependent reactivation (Phase II); and (ii) a histone methyl/phospho switch during Phase I is required for Phase II reactivation. The challenge to the field is reconciling these data into a unified model of virus reactivation. The task of compiling this review was uncomfortably humbling, as if cataloging the stars in the universe. While not completely dark, our night sky is missing a multitude of studies which are among the many points of light contributing to our field. This article is a focused review in which we discuss from the vantage point of our expertise, just a handful of concepts that have or are emerging. A lookback at some of the pioneering work that grounds our field is also included.

中文翻译：

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以单纯疱疹病毒为重点的 Alphaherpesvirus 潜伏期和再激活。

我们正处于了解 alpha 疱疹病毒潜伏期和再激活及其对人类疾病的影响的有趣时期。概念上的进步来自动物和神经元培养模型。这篇综述着重于表皮蛋白和病毒反式激活因子 VP16 在从潜伏期到裂解周期的转变中起主要作用的概念。在急性感染期间，VP16 反式激活的调节平衡了在神经系统中的传播、潜伏感染的建立和毒力。重新激活依赖于这种反式激活因子来驱动进入裂解循环。VP16 蛋白的体内从头表达由嵌入在通常渗漏的晚期启动子中的赋予预立即早期转录的序列介导。体外，在潜伏期调节 VP16 表达的替代机制来自 SCG 神经元培养模型，包括以下概念：（i）病毒基因组的普遍转录去抑制和 VP16 在细胞质中隔离约 48 小时（第一阶段）之前和需要 VP16 依赖性再激活（第二阶段）；(ii) 阶段 I 的组蛋白甲基/磷酸转换是阶段 II 重新激活所必需的。该领域面临的挑战是将这些数据调和为病毒重新激活的统一模型。编写这篇评论的任务是令人不安的谦卑，仿佛在对宇宙中的星星进行分类。虽然不是完全黑暗，但我们的夜空缺少大量研究，这些研究是为我们的领域做出贡献的众多亮点之一。本文是一篇重点回顾，我们从专业知识的角度讨论了一些已经或正在出现的概念。还包括回顾我们领域的一些开创性工作。