UC Berkeley-UCSF Joint Medical Program, Berkeley, CA, USA.
Wageningen Bioveterinary Institute, Lelystad and Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
Methods Mol Biol. 2023;2682:191-204. doi: 10.1007/978-1-0716-3283-3_14.
The development of humanized mouse models has recently opened new avenues in the field of infectious diseases. These models allow research on many human viruses that were once difficult to study, because finding suitable animal models of infection can be challenging, cost prohibitive, and often do not entirely recapitulate all parameters of the disease. Here, we describe the procedure of human immune system reconstitution (humanization) of NOD.Cg-Prkdc Il2rg/SzJ (NSG) mice by the bone marrow, liver, and thymus (BLT) reconstitution method as well as the process of human lung engraftment. We then describe how to infect these human lung grafts with the paramyxovirus Nipah virus (NiV) that can cause lethal respiratory disease in humans, and for which there is only limited understanding of pathogenesis to acute lung injury.
近年来,人性化小鼠模型的发展为传染病领域开辟了新的途径。这些模型允许对许多曾经难以研究的人类病毒进行研究,因为寻找合适的感染动物模型可能具有挑战性、成本高昂,而且通常无法完全再现疾病的所有参数。在这里,我们描述了通过骨髓、肝脏和胸腺(BLT)重建方法对 NOD.Cg-Prkdc Il2rg/SzJ(NSG)小鼠进行人免疫系统重建(人源化)的过程,以及人肺移植的过程。然后,我们描述了如何用人副黏病毒尼帕病毒(NiV)感染这些人肺移植物,尼帕病毒可导致人类致命呼吸道疾病,而对于尼帕病毒引起急性肺损伤的发病机制,目前仅有有限的了解。