在免疫细胞中表达1型人类免疫缺陷病毒的转基因小鼠会患上严重的艾滋病样疾病。
Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease.
作者信息
Hanna Z, Kay D G, Cool M, Jothy S, Rebai N, Jolicoeur P
机构信息
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Quebec, Canada.
出版信息
J Virol. 1998 Jan;72(1):121-32. doi: 10.1128/JVI.72.1.121-132.1998.
Abstract
We have constructed transgenic (Tg) mice expressing the entire human immunodeficiency virus type 1 (HIV-1) coding sequences in cells targeted by HIV-1 infection in humans. These Tg mice developed a severe AIDS-like disease leading to early death (< 1 month). They developed muscle wasting, severe atrophy and fibrosis of lymphoid organs, tubulointerstitial nephritis, and lymphoid interstitial pneumonitis. In addition the expression of RANTES was increased in various tissues of these Tg mice relative to that in the normal controls. Disease appearance was correlated with the levels of transgene expression. The numerous pathologies observed in these mice are remarkably similar to those observed in human AIDS and, more specifically, in pediatric AIDS.
摘要
我们构建了转基因（Tg）小鼠，其在人类中受HIV-1感染的靶向细胞中表达完整的人类免疫缺陷病毒1型（HIV-1）编码序列。这些Tg小鼠发展出严重的艾滋病样疾病，导致早期死亡（<1个月）。它们出现肌肉消瘦、淋巴器官严重萎缩和纤维化、肾小管间质性肾炎以及淋巴间质性肺炎。此外，相对于正常对照，这些Tg小鼠各种组织中RANTES的表达增加。疾病表现与转基因表达水平相关。在这些小鼠中观察到的众多病理与在人类艾滋病中观察到的病理非常相似，更具体地说，与儿童艾滋病中观察到的病理相似。
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本文引用的文献
1
HIV-1 and the thymus.
AIDS. 1997 Mar 15;11(4):403-14. doi: 10.1097/00002030-199704000-00002.
2
Early cytokine and chemokine gene expression in lymph nodes of macaques infected with simian immunodeficiency virus is predictive of disease outcome and vaccine efficacy.
J Virol. 1997 Feb;71(2):1227-36. doi: 10.1128/JVI.71.2.1227-1236.1997.
3
Host factors and the pathogenesis of HIV-induced disease.
Nature. 1996 Dec 12;384(6609):529-34. doi: 10.1038/384529a0.
4
HIV replication in CD4+ T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous beta-chemokines and the viral inductive effects of other endogenous cytokines.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14076-81. doi: 10.1073/pnas.93.24.14076.
5
Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis.
Am J Pathol. 1996 Nov;149(5):1459-67.
6
Human immunodeficiency-virus-related pulmonary infections in children.
Semin Respir Infect. 1996 Sep;11(3):173-83.
7
Early progression of disease in HIV-infected infants with thymus dysfunction.
N Engl J Med. 1996 Nov 7;335(19):1431-6. doi: 10.1056/NEJM199611073351904.
8
Models of HIV type 1 proviral gene expression in wild-type HIV and MLV/HIV transgenic mice.
AIDS Res Hum Retroviruses. 1996 Aug 10;12(12):1103-16. doi: 10.1089/aid.1996.12.1103.
9
HIV type 1 Nef perturbs eye lens development in transgenic mice.
AIDS Res Hum Retroviruses. 1996 Feb 10;12(3):177-89. doi: 10.1089/aid.1996.12.177.
10
Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease.
J Pathol. 1996 Feb;178(2):201-6. doi: 10.1002/(SICI)1096-9896(199602)178:2<201::AID-PATH440>3.0.CO;2-4.
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