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登革病毒感染HepG2-严重联合免疫缺陷小鼠模型的建立

Development of HepG2-severe combined immunodeficiency mouse model for dengue virus infection
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摘要 缺乏合适的动物模型严重限制了登革病毒(DENV)致病机制研究的进展。本研究旨在构建DENV感染小鼠模型,为阐明其致病机制提供实验材料。首先在严重联合免疫缺陷(SCID)小鼠腹腔内接种人肝癌细胞株HepG2,构建人鼠嵌合体动物模型;移植后10d腹腔接种DENV,通过检测病毒在体内分布及主要器官的组织学改变,评价该动物模型的实用价值。结果显示,在SCID小鼠成功移植HepG2并感染DENV后,出现病毒血症及主要器官严重损伤等现象,但无后肢麻痹等人类登革热无关症状。本研究成功构建了HepG2-SCID人鼠嵌合模型,该模型能支持DENV复制,并表现出部分人类DENV感染的临床症状,为研究DENV的致病机制提供了有价值的实验材料。 The purpose of the current study is to develop a mouse model for exploration of the pathogenesis of dengue virus （DENV） infection. HepG2 cells were transplanted to severe combined immunodeficiency （SCID） mice intraperitoneally to develop a HepG2-SCID mouse chimera model. To confirm the successful transplantation, the concentration of human albumin （hALB） in the serum was determined by sandwich enzyme-linked immunosorbent assay. Following challenge with intraperitoneal injection of DENV2, HepG2- SCID mice were evaluated by detection of virus distribution and histological changes in major organs. HepG2 cells engrafted into SCID mouse could support the replication of DENV2. HepG2-SCID mouse showed viremia and severe organ injuries. The data suggest that DENV2-infected HepG2-SCID chimera model is developed successfully, which would provide a useful tool for studying pathogenesis of DENV infection.
作者 陈艳雷 王娟 高娜 范东瀛 王一松 安静
机构地区 首都医科大学基础医学院微生物学教研室
出处 《微生物与感染》 2013年第1期16-20,共5页 Journal of Microbes and Infections
基金 国家自然科学基金(81271839)
关键词 登革病毒 动物模型HepG2细胞株 Dengue virus Animal model HepG2 cell
分类号 R-332 [医药卫生]
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参考文献18

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二级参考文献9

  • 1Cassetti MC,Durbin A,Harris E,et al.Report of an NIAID workshop on dengue animal models[J].Vaccine,2010,28(26):4229-4234.
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  • 3Blaney JE Jr,Johnson DH,Manipon GG,et al.Genetic basis of attenuation of Dengue virus type 4 small plaque mutants with restricted replication in suckling mice and in SCID mice transplanted with human liver cells[J].Virology,2002,300(1):125-139.
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  • 5Shresta S,Sharar KL,Prigozhin DM,et al.Murine model for dengue virus-induced lethal disease with increased vascular permeability[J].J Virol,2006,80(20):10208-10217.
  • 6Huang KJ,Li SY,Chen SC,et al.Manifestation of thrombocytopenia in dengue-2-virus-infected mice[J].J Gen Virol,2000,81(Pt 9):2177-2182.
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  • 9盛子洋,王娟,吴江漫,安静,范东瀛.利用甲基纤维素改良的病毒噬斑技术[J].免疫学杂志,2012,28(4):363-365. 被引量：3
微生物与感染
2013年 第1期

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