Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.
Viruses. 2019 Jan 26;11(2):103. doi: 10.3390/v11020103.
Varicella zoster virus (VZV) is a highly prevalent human pathogen that causes varicella (chicken pox) during primary infection and establishes latency in peripheral neurons. Symptomatic reactivation often presents as zoster (shingles), but it has also been linked to life-threatening diseases such as encephalitis, vasculopathy and meningitis. Zoster may be followed by postherpetic neuralgia, neuropathic pain lasting after resolution of the rash. The mechanisms of varicella zoster virus (VZV) latency and reactivation are not well characterized. This is in part due to the human-specific nature of VZV that precludes the use of most animal and animal-derived neuronal models. Recently, in vitro models of VZV latency and reactivation using human neurons derived from stem cells have been established facilitating an understanding of the mechanisms leading to VZV latency and reactivation. From the models, c-Jun N-terminal kinase (JNK), phosphoinositide 3-kinase (PI3K) and nerve growth factor (NGF) have all been implicated as potential modulators of VZV latency/reactivation. Additionally, it was shown that the vaccine-strain of VZV is impaired for reactivation. These models may also aid in the generation of prophylactic and therapeutic strategies to treat VZV-associated pathologies. This review summarizes and analyzes the current human neuronal models used to study VZV latency and reactivation, and provides some strategies for their improvement.
水痘带状疱疹病毒（VZV）是一种高度流行的人类病原体，在初次感染时会引起水痘（水痘），并在周围神经元中建立潜伏状态。症状性再激活常表现为带状疱疹（带状疱疹），但也与危及生命的疾病有关，如脑炎、血管病和脑膜炎。带状疱疹可能会导致带状疱疹后神经痛，即在皮疹消退后持续存在的神经病理性疼痛。水痘带状疱疹病毒（VZV）潜伏和再激活的机制尚未得到很好的描述。这在一定程度上是由于 VZV 的人类特异性，排除了大多数动物和动物源性神经元模型的使用。最近，使用源自干细胞的人类神经元建立了 VZV 潜伏和再激活的体外模型，有助于了解导致 VZV 潜伏和再激活的机制。从这些模型中，c-Jun N-末端激酶（JNK）、磷酸肌醇 3-激酶（PI3K）和神经生长因子（NGF）都被认为是 VZV 潜伏/再激活的潜在调节剂。此外，还表明 VZV 的疫苗株在再激活方面存在缺陷。这些模型也可能有助于生成预防和治疗策略来治疗与 VZV 相关的病理。本文综述并分析了目前用于研究 VZV 潜伏和再激活的人类神经元模型，并提供了一些改进这些模型的策略。
