Dengue Virus Tropism in Humanized Mice Recapitulates Human Dengue Fever

Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans.登革病毒疾病的动物模型开发历来极具挑战性，这是由于该病毒仅能在特定人类细胞中完成感染与复制过程。我们通过将脐带血来源的人类干细胞移植至免疫缺陷小鼠体内，成功构建了登革热人源化小鼠模型。该模型小鼠可出现与人类登革热患者一致的可观测病症：发热、病毒血症、红斑以及血小板减少症；当感染登革病毒血清型2（Dengue Serotype 2）的强毒株后，小鼠体内骨髓、脾脏与血液中的人类细胞均可被病毒感染。被感染的人类细胞会向小鼠血液循环中分泌细胞因子与趋化因子。本研究证实，该小鼠模型中登革病毒感染的病理进程与人类患者的临床报道一致，这也是首个可用于研究人类登革热发病机制的有效且贴合临床的动物模型。