Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
Curr Top Microbiol Immunol. 2023;438:135-161. doi: 10.1007/82_2022_255.
Varicella-zoster virus (VZV) is a human-restricted virus, which raises obstacles to research. The strict human tropism limits knowledge about its pathogenesis and creates challenges for evaluating antiviral treatments and vaccines. The development of humanized mouse models was driven by the need to address these challenges. Here, we summarize the humanized mouse models with xenografts of thymus/liver organoids, skin, dorsal root ganglia, and lung tissues. These models revealed VZV ORFs involved in cell tropism and pathogenesis in differentiated tissues, and made it possible to evaluate antiviral compounds in a mammalian system. Further development of skin organ culture techniques have the added benefit of lower cost and greater speed than mouse models. Human tissues, both in humanized mice and in ex vivo models, will continue to be necessary to study VZV in the tissue microenvironements to which it is adapted.
水痘-带状疱疹病毒（VZV）是一种局限于人类的病毒，这给研究带来了障碍。严格的人类嗜性限制了人们对其发病机制的了解，并为评估抗病毒治疗方法和疫苗带来了挑战。为了应对这些挑战，人们开发了人源化小鼠模型。本文总结了带有胸腺/肝脏类器官、皮肤、背根神经节和肺组织异种移植物的人源化小鼠模型。这些模型揭示了 VZV ORF 在分化组织中对细胞嗜性和发病机制的作用，并使在哺乳动物系统中评估抗病毒化合物成为可能。皮肤类器官培养技术的进一步发展具有比小鼠模型更低的成本和更高的速度的优势。人类组织，无论是在人源化小鼠还是在离体模型中，都将继续用于研究适应其组织微环境的 VZV。
