Microglia from mice transgenic for a provirus encoding a monocyte-tropic HIV type 1 isolate produce infectious virus and display in vitro and in vivo upregulation of lipopolysaccharide-induced chemokine gene expression.
Microglia from mice transgenic for a provirus encoding a monocyte-tropic HIV type 1 isolate produce infectious virus and display in vitro and in vivo upregulation of lipopolysaccharide-induced chemokine gene expression.
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来自编码单核细胞嗜性 HIV 1 分离株的原病毒转基因小鼠的小胶质细胞产生感染性病毒，并在体外和体内表现出脂多糖诱导的趋化因子基因表达的上调。
DOI：
10.1089/088922203769232557
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发表时间：
2003
影响因子：
1.5
通讯作者：
Goldstein,Harris
中科院分区：
文献类型：
--
作者：
Wang,Emilie-Jeanne;Sun,Jinglin;Pettoello-Mantovani,Massimo;Anderson,ChristinaM;Osiecki,Kristin;Zhao,Meng-Liang;Lopez,Lillie;Lee,SunheeChoi;Berman,JoanW;Goldstein,Harris
A large body of evidence has indicated that microglia are the predominant cellular location for HIV-1 in the brains of HIV-1-infected individuals and play a direct role in the development of HIV-1-associated dementia (HAD). Therefore, investigation of the mechanism by which HIV-1-infected microglia contribute to the development of HIV-associated dementia should be facilitated by the creation of a mouse model wherein microglia carry replication-competent HIV-1. To circumvent the inability of HIV-1 to infect mouse cells, we developed a mouse line that is transgenic for a full-length proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1JR-CSF(JR-CSF mice), whose T cells and monocytes produce infectious HIV-1. We detected expression of the long terminal repeat-regulated proviral transgene in the microglia of these transgenic mice and demonstrated that it was increased byin vitroandin vivostimulation with lipopolysaccharide. Furthermore, microglia isolated from JR-CSF mouse brains produced HIV-1 that was infectiousin vitroandin vivo. We examined the effect that carriage of the HIV-1 provirus had on chemokine gene regulation in the brains of these mice and demonstrated that MCP-1 gene expression by JR-CSF mouse microglia and brains was more responsive toin vitroandin vivostimulation with lipopolysaccharide than were microglia and brains from control mice. Thus, this study indicates that the JR-CSF mice may represent a new mouse model to study the effect of HIV-1 replication on microglia function and its contribution to HIV-1-associated neurological disease.
