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从一名患有慢性神经疾病患者的外周淋巴细胞DNA中克隆人I型嗜T细胞淋巴细胞病毒样前病毒基因组。

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders.

作者信息

Reddy E P, Mettus R V, DeFreitas E, Wroblewska Z, Cisco M, Koprowski H

机构信息

Wistar Institute, Philadelphia, PA 19104.

出版信息

Proc Natl Acad Sci U S A. 1988 May;85(10):3599-603. doi: 10.1073/pnas.85.10.3599.

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome.

摘要

人类嗜T细胞病毒1型(HTLV-I)是人类T细胞白血病的病原体,最近已被证明与神经系统疾病有关,如热带痉挛性截瘫、HTLV相关脊髓病,还可能与多发性硬化症有关。在本报告中,我们研究了一例可归类为多发性硬化症或热带痉挛性截瘫的特定神经系统疾病病例。发现该患有慢性神经系统疾病的患者血清和脑脊液中含有针对HTLV-I包膜蛋白和gag蛋白的抗体。通过原位杂交显示,患者外周血和脑脊液中的淋巴细胞表达病毒RNA序列。对患者淋巴细胞DNA的Southern印迹分析显示存在HTLV-I相关序列。对白介素2刺激的新鲜外周淋巴细胞的RNA进行印迹杂交分析,结果显示存在大量基因组病毒RNA,亚基因组RNA很少或没有。我们从外周淋巴细胞的DNA中克隆了前病毒基因组,并确定了其限制酶切图谱。该分析表明,这个前病毒基因组即使与原型HTLV-I基因组不完全相同,也非常相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b9a/280261/2bff6f37ab70/pnas00262-0338-a.jpg

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