When herpes simplex virus 1 (HSV-1) infection is initiated in the ocular, nasal, or oral cavity, sensory neurons within trigeminal ganglia (TG) become infected. Following a burst of viral transcription in TG neurons, lytic cycle viral genes are suppressed and latency is established. The latency-associated transcript (LAT) is the only viral gene abundantly expressed during latency, and LAT expression is important for the latency-reactivation cycle. Reactivation from latency is required for virus transmission and recurrent disease, including encephalitis. The Wnt/β-catenin signaling pathway is differentially expressed in TG during the bovine herpesvirus 1 latency-reactivation cycle. Hence, we hypothesized HSV-1 regulates the Wnt/β-catenin pathway and promotes maintenance of latency because this pathway enhances neuronal survival and axonal repair. New studies revealed β-catenin was expressed in significantly more TG neurons during latency compared to TG from uninfected mice or mice latently infected with a LAT-/- mutant virus. When TG explants were incubated with media containing dexamethasone to stimulate reactivation, significantly fewer β-catenin+ TG neurons were detected. Conversely, TG explants from uninfected mice or mice latently infected with a LAT-/- mutant increased the number of β-catenin+ TG neurons in the presence of DEX relative to samples not treated with DEX. Impairing Wnt signaling with small molecule antagonists reduced virus shedding during explant-induced reactivation. These studies suggested β-catenin was differentially expressed during the latency-reactivation cycle, in part due to LAT expression.

中文翻译：

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单纯疱疹病毒 1 在潜伏-再激活周期中调节 TG 神经元中 β-连环蛋白的表达。

当单纯疱疹病毒 1 (HSV-1) 感染在眼、鼻或口腔中开始时，三叉神经节 (TG) 内的感觉神经元被感染。在 TG 神经元中病毒转录爆发后，裂解循环病毒基因被抑制并建立潜伏期。潜伏期相关转录本 (LAT) 是唯一在潜伏期大量表达的病毒基因，并且 LAT 表达对于潜伏-再激活周期很重要。病毒传播和复发性疾病（包括脑炎）需要从潜伏期重新激活。Wnt/β-catenin 信号通路在牛疱疹病毒 1 潜伏-再激活周期期间在 TG 中差异表达。因此，我们假设 HSV-1 调节 Wnt/β-catenin 通路并促进延迟的维持，因为该通路增强了神经元存活和轴突修复。新研究表明，与来自未感染小鼠或潜伏感染 LAT-/- 突变病毒的小鼠的 TG 相比，β-连环蛋白在潜伏期间在更多的 TG 神经元中表达。当 TG 外植体与含有地塞米松的培养基一起培养以刺激再激活时，检测到的 β-连环蛋白 + TG 神经元显着减少。相反，与未用 DEX 处理的样品相比，来自未感染小鼠或潜在感染 LAT-/- 突变体的小鼠的 TG 外植体在 DEX 存在下增加了 β-连环蛋白 + TG 神经元的数量。用小分子拮抗剂削弱 Wnt 信号会减少外植体诱导的再激活过程中的病毒脱落。这些研究表明 β-连环蛋白在潜伏-再激活周期中差异表达，部分原因是 LAT 表达。