Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA 94305, USA.
J Neurovirol. 2011 Dec;17(6):570-7. doi: 10.1007/s13365-011-0066-x. Epub 2011 Dec 8.
Varicella-zoster virus (VZV) is a medically important human alphaherpesvirus. Investigating pathogenic mechanisms that contribute to VZV neurovirulence are made difficult by a marked host restriction. Our approach to investigating VZV neurotropism and neurovirulence has been to develop a mouse-human xenograft model in which human dorsal root ganglia (DRG) are maintained in severe compromised immunodeficient (SCID) mice. In this review, we will describe our key findings using this model in which we have demonstrated that VZV infection of SCID DRG xenograft results in rapid and efficient spread, enabled by satellite cell infection and polykaryon formation, which facilitates robust viral replication and release of infectious virus. In neurons that persist following this acute replicative phase, VZV genomes are present at low frequency with limited gene transcription and no protein synthesis, a state that resembles VZV latency in the natural human host. VZV glycoprotein I and interaction between glycoprotein I and glycoprotein E are critical for neurovirulence. Our work demonstrates that the DRG model can reveal characteristics about VZV replication and long-term persistence of latent VZV genomes in human neuronal tissues, in vivo, in an experimental system that may contribute to our knowledge of VZV neuropathogenesis.
水痘-带状疱疹病毒（VZV）是一种医学上重要的人类α疱疹病毒。由于宿主的明显限制，研究导致 VZV 神经毒力的发病机制变得困难。我们研究 VZV 嗜神经性和神经毒力的方法是开发一种鼠-人异种移植模型，其中人类背根神经节（DRG）在严重免疫缺陷（SCID）小鼠中维持。在这篇综述中，我们将描述我们使用该模型的关键发现，我们已经证明 VZV 感染 SCID DRG 异种移植物会导致快速和有效的传播，这得益于卫星细胞感染和多核形成，从而促进了强大的病毒复制和传染性病毒的释放。在急性复制阶段后持续存在的神经元中，VZV 基因组以低频率存在，转录有限，没有蛋白质合成，这种状态类似于天然人类宿主中的 VZV 潜伏。VZV 糖蛋白 I 和糖蛋白 I 与糖蛋白 E 之间的相互作用对于神经毒力至关重要。我们的工作表明，DRG 模型可以揭示 VZV 复制的特征以及潜伏 VZV 基因组在人类神经元组织中的长期持续存在，在体内，在实验系统中，这可能有助于我们了解 VZV 神经发病机制。
