Humanized Severe Combined Immunodeficient (SCID) Mouse Models for Varicella-Zoster Virus Pathogenesis

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.