Gutierrez-Barbosa Hernando, Medina-Moreno Sandra, Davis Harry, Bryant Joseph, Chua Joel V, Zapata Juan C
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Grupo de Virología, Vicerrectoría de Investigaciones, Universidad El Bosque, Bogotá, Colombia.
Methods Mol Biol. 2022;2409:271-289. doi: 10.1007/978-1-0716-1879-0_19.
Dengue is one of the most prevalent infectious diseases around the world, present in all continents and mainly affecting developing countries. With few tools to fight and study this disease, it is imperative to have reliable animal models that not only recapitulate human disease but also contain human components to understand the pathogenic mechanism and immune responses, allowing the development of new treatments and vaccines against dengue. Humanized mice are a significant advance in the development of in vivo models to understanding the relation of the human immune system and target organs such as the liver during the infection by dengue virus, allowing basic and preclinical research. In this chapter, we describe the use of humanized NSG mice (huNSG) for the study of dengue disease. The first model describes reconstitution of the human immune system by transplanting human CD34 stem cells in newborn or adult NSG mice. The second model combines the reconstitution with CD34 stem cells with the transplant of human primary hepatocytes. This dual reconstituted animal will have two of the major players involved in the development of dengue infection. However, there are still more biological components missing in this model for dengue, but researchers continue working to improve the huNSG model to reconstitute other human components.
登革热是全球最普遍的传染病之一，在各大洲均有出现，主要影响发展中国家。由于对抗和研究这种疾病的工具匮乏，拥有可靠的动物模型至关重要，这些模型不仅要能重现人类疾病，还应包含人类成分，以了解致病机制和免疫反应，从而推动新型登革热治疗方法和疫苗的研发。人源化小鼠是体内模型发展的一项重大进展，有助于理解登革病毒感染期间人类免疫系统与肝脏等靶器官之间的关系，从而开展基础研究和临床前研究。在本章中，我们描述了使用人源化NSG小鼠（huNSG）研究登革热疾病的方法。第一个模型描述了通过将人类CD34干细胞移植到新生或成年NSG小鼠中来重建人类免疫系统。第二个模型将CD34干细胞的重建与人类原代肝细胞的移植相结合。这种双重重建的动物将拥有参与登革热感染发展的两个主要参与者。然而，该登革热模型仍缺少更多生物成分，但研究人员仍在继续努力改进huNSG模型以重建其他人类成分。
