Generation and Characterization of a Humanized Lung Xenograft Mouse Model for Studying Henipavirus Pathogenesis

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^scid Il2rg^tm1Wjl/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.