Transgenic dissection of HIV genes involved in lymphoid depletion.
Transgenic dissection of HIV genes involved in lymphoid depletion.
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涉及淋巴耗竭的 HIV 基因的转基因解剖。
DOI：
10.1172/jci119518
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Jay,G
中科院分区：
文献类型：
--
作者：
Tinkle,BT;Ueda,H;Ngo,L;Luciw,PA;Shaw,K;Rosen,CA;Jay,G
携带HIV前病毒的转基因小鼠，选择性删除所有三个结构基因，产生了广泛的淋巴耗竭，不仅在脾脏和淋巴结中检测到，而且在胸腺中也检测到。具有高水平HIV基因表达的小鼠发展为急性疾病，导致过早死亡，而具有低水平病毒转录物的小鼠发展为慢性疾病，长期存活。HIV复制和包膜糖蛋白（gp120）都不需要T细胞耗竭。尽管在生命早期有丰富的病毒基因表达，但细胞死亡直到淋巴细胞完全成熟时才变得明显，这表明胸腺生成不受影响。外周淋巴器官和胸腺髓质中的成熟T细胞对凋亡过程的敏感性低于胸腺皮质中的未成熟T细胞。外周淋巴器官中T细胞区室的逐渐耗竭密切伴随着B细胞区室的相互扩增，导致淋巴结中T淋巴细胞几乎完全被B免疫母细胞取代。不像T细胞显示出丰富的HIV基因表达，B细胞没有。转基因方法可能有助于识别HIV非结构基因（S）负责免疫缺陷，并有助于促进解剖其在诱导细胞凋亡中的作用。
Transgenic mice carrying an HIV provirus, with selective deletion of all three structural genes, developed extensive lymphoid depletion which was detected not only in the spleen and lymph nodes but also in the thymus. Mice with a high level of HIV gene expression developed acute disease which resulted in premature death, and mice with a low level of viral transcripts developed chronic disease with long-term survival. Neither HIV replication nor the envelope glycoprotein (gp120) was required for T cell depletion. Despite abundant viral gene expression early in life, cell death did not become evident until about the time of full lymphoid maturation, suggesting that thymopoiesis was not affected. The more mature T cells in the peripheral lymphoid organs and in the thymic medulla were less sensitive to the apoptotic process than the immature T cells in the thymic cortex. Gradual depletion of the T cell compartment in the peripheral lymphoid organs was intimately accompanied by the reciprocal expansion of the B cell compartment, resulting in the almost complete replacement of T lymphocytes with B immunoblasts in lymph nodes. Unlike T cells, which showed abundant HIV gene expression, B cells did not. The transgenic approach may help identify the HIV nonstructural gene(s) responsible for immune deficiency and help facilitate dissection of its role in inducing apoptosis.