Selective expression of human immunodeficiency virus Nef in specific immune cell populations of transgenic mice is associated with distinct AIDS-like phenotypes.
Selective expression of human immunodeficiency virus Nef in specific immune cell populations of transgenic mice is associated with distinct AIDS-like phenotypes.
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人类免疫缺陷病毒 Nef 在转基因小鼠特定免疫细胞群中的选择性表达与独特的艾滋病样表型相关。
DOI：
10.1128/jvi.00125-09
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发表时间：
2009
影响因子：
5.4
通讯作者：
Jolicoeur,Paul
中科院分区：
文献类型：
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作者：
Hanna,Zaher;Priceputu,Elena;Chrobak,Pavel;Hu,Chunyan;Dugas,Véronique;Goupil,Mathieu;Marquis,Miriam;deRepentigny,Louis;Jolicoeur,Paul
我们之前报道过，CD4C/人类免疫缺陷病毒（HIV）Nef转基因（Tg）小鼠在CD4+T细胞和巨噬细胞/树突状细胞（DC）谱系的细胞中表达Nef，会发展出一种严重的艾滋病样疾病，其特征是CD4+T细胞耗竭，以及肺、心脏和肾脏疾病。为了确定不同的造血细胞群对这种艾滋病样疾病的发展的贡献，另外产生了五种通过限制性细胞特异性调控元件表达 Nef 的 Tg 菌株。这些 Tg 菌株在 CD4+T 细胞、DC 和巨噬细胞 (CD4E/HIVNef) 中表达 Nef； CD4+T 细胞和 DC（mCD4/HIVNef 和 CD4F/HIVNef）；巨噬细胞和 DC（CD68/HIVNef）；或主要存在于 DC（CD11c/HIVNef）中。这些 Tg 菌株均未出现明显的肺和肾疾病，这表明存在尚未鉴定的表达 Nef 的细胞亚群，这些细胞亚群负责诱导 CD4C/HIVNefTg 小鼠的器官疾病。所有五种品系的小鼠都出现了持续口腔携带白色念珠菌的情况，表明免疫功能受损。只有在 CD4+T 细胞中表达 Nef 的菌株才表现出 CD4+T 细胞的耗竭、激活和凋亡。这些结果证明 CD4+T 细胞中 Nef 的表达是其耗竭的主要决定因素。因此，特定细胞群中 Nef 表达的模式在很大程度上决定了由此产生的病理变化的性质。
We previously reported that CD4C/human immunodeficiency virus (HIV)Neftransgenic (Tg) mice, expressing Nef in CD4+T cells and cells of the macrophage/dendritic cell (DC) lineage, develop a severe AIDS-like disease, characterized by depletion of CD4+T cells, as well as lung, heart, and kidney diseases. In order to determine the contribution of distinct populations of hematopoietic cells to the development of this AIDS-like disease, five additional Tg strains expressing Nef through restricted cell-specific regulatory elements were generated. These Tg strains express Nef in CD4+T cells, DCs, and macrophages (CD4E/HIVNef); in CD4+T cells and DCs (mCD4/HIVNefand CD4F/HIVNef); in macrophages and DCs (CD68/HIVNef); or mainly in DCs (CD11c/HIVNef). None of these Tg strains developed significant lung and kidney diseases, suggesting the existence of as-yet-unidentified Nef-expressing cell subset(s) that are responsible for inducing organ disease in CD4C/HIVNefTg mice. Mice from all five strains developed persistent oral carriage ofCandida albicans, suggesting an impaired immune function. Only strains expressing Nef in CD4+T cells showed CD4+T-cell depletion, activation, and apoptosis. These results demonstrate that expression of Nef in CD4+T cells is the primary determinant of their depletion. Therefore, the pattern of Nef expression in specific cell population(s) largely determines the nature of the resulting pathological changes.