登革热病毒SCID-LO2人鼠嵌合模型的建立与评价

目的构建登革热病毒(DENV)感染的小动物模型,为阐明其致病机制提供实验材料。方法向严重联合免疫缺陷(SCID)小鼠腹腔内接种人正常肝细胞(LO2)构建"人鼠嵌合体"动物模型,进而腹腔注射DENV,通过检查病毒在体内分布和主要器官的组织学改变,对DENV感染的动物模型进行评价。结果 SCID小鼠成功移植LO2,并且嵌合小鼠感染DENV后出现病毒血症及严重的器官损伤等表现,但无后肢麻痹等无关症状。结论成功构建了SCID-LO2人鼠嵌合模型,嵌合小鼠能够支持DENV复制,并表现出部分人类感染DENV的临床症状,该小鼠感染模型为研究DENV的致病机制提供了有价值的实验材料。

Development and evaluation of Dengue virus infected SCID-LO2 chimeric mouse model

Objective To develop a mouse model for exploration of the pathogenesis of Dengue virus(DENV) infection.Methods Human normal hepatic cell line LO2 was transplanted to severe combined immunodeficiency(SCID) mice intraperitoneally to develop a SCID-LO2 chimeric mouse model.Following challenge with intraperitoneally injected DENV,the model was evaluated based on virus distribution and the histological changes of main organs.Results The LO2 cells were successfully engrafted into SCID mice.SCID-LO2 chimeric mice showed viremia and severe organ injury after the infection of DENV,but without hind-leg paralysis.Conclusion SCID-LO2 chimeric mice can maintain the replication of DENV and manifest some clinical symptoms of DENV infection in humans.Therefore,the SCID-LO2 chimeric mouse model is valuable for studying the pathogenic mechanism of DENV infection.