Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, 1 Barker Hall, Berkeley, CA 94720, USA.
Viruses. 2012 Jan;4(1):62-82. doi: 10.3390/v4010062. Epub 2012 Jan 9.
The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the 'vascular-leak' syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.
登革病毒（DENV）感染和疾病的动物模型的发展一直具有挑战性，因为流行的 DENV 不会自然感染非人类物种。非人类灵长类动物（NHPs）可以在相关细胞类型中维持病毒复制并产生强大的免疫反应，但它们不会出现明显的疾病。相比之下，某些感染了适应小鼠的 DENV 株的免疫缺陷型小鼠模型显示出类似于人类重症登革热中出现的“血管渗漏”综合征的严重疾病迹象。人源化小鼠模型可以维持 DENV 的复制并显示出一些疾病迹象，但需要进一步发展来验证免疫反应。经典的，感染 DENV 的免疫功能正常的小鼠不会出现疾病，否则当脑内接种时会出现瘫痪；然而，最近已经证明，使用高剂量 DENV 的一种新模型在感染后会出现出血迹象。总的来说，每种模型都有其优缺点，并且在登革热发病机制和免疫发病机制的研究以及/或抗病毒药物和疫苗的临床前测试方面具有不同的适用性。
