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在含有表达Fv4-env的造血细胞的转基因小鼠和骨髓嵌合小鼠中对逆转录病毒感染的抗性。

Resistance to retroviral infection in transgenic and bone marrow chimeric mice containing Fv4-env-expressing hematopoietic cells.

作者信息

Limjoco T, Nihrane A, Silver J

机构信息

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Virology. 1995 Apr 1;208(1):75-83. doi: 10.1006/viro.1995.1131.

DOI:10.1006/viro.1995.1131
PMID:11831733
Abstract

Mice and chickens that inherit certain retroviral envelope genes are resistant to infection with related retroviruses. Previously, we described two transgenic mouse strains bearing a retroviral envelope gene, Fv4, that confers resistance to infection with ecotropic retroviruses (T. I. Limjoco et al., 1993, J. Virol. 67, 4163-4168). Here, we present results with these and an additional transgenic strain that show that (1) the level of resistance is correlated with level of expression of the transgene, (2) low-level expression of the transgene is associated with an unexpected and possibly immune-mediated phenotype of recovery from viremia, (3) resistance can be transferred by bone marrow transplantation and is "dominant" in chimeras containing mixtures of transgenic resistant plus control bone marrow, and (4) transplantation after infection with Friend Virus is much less effective than transplantation before infection. We discuss the implications of these results for gene therapy of retroviral infection.

摘要

继承某些逆转录病毒包膜基因的小鼠和鸡对相关逆转录病毒感染具有抗性。此前,我们描述了两种携带逆转录病毒包膜基因Fv4的转基因小鼠品系,该基因赋予了对嗜亲性逆转录病毒感染的抗性(T.I. Limjoco等人,1993年,《病毒学杂志》67卷,4163 - 4168页)。在此,我们展示了这些以及另一个转基因品系的结果,表明:(1)抗性水平与转基因的表达水平相关;(2)转基因的低水平表达与从病毒血症中恢复的一种意想不到且可能是免疫介导的表型相关;(3)抗性可通过骨髓移植转移,并且在含有转基因抗性骨髓与对照骨髓混合物的嵌合体中是“显性的”;(4)感染弗氏病毒后进行移植比感染前移植效果差得多。我们讨论了这些结果对逆转录病毒感染基因治疗的意义。

相似文献

1
Resistance to retroviral infection in transgenic and bone marrow chimeric mice containing Fv4-env-expressing hematopoietic cells.在含有表达Fv4-env的造血细胞的转基因小鼠和骨髓嵌合小鼠中对逆转录病毒感染的抗性。
Virology. 1995 Apr 1;208(1):75-83. doi: 10.1006/viro.1995.1131.
2
Distribution of Fv-4 resistant gene product in Friend leukemia virus-resistant Fv-4r mouse strain.Fv-4抗性基因产物在抗Friend白血病病毒的Fv-4r小鼠品系中的分布。
Exp Hematol. 1996 Oct;24(12):1423-31.
3
Bone marrow transplantation from Fv-4-resistant donors rescues Friend leukemia virus-infected mice from leukemia: a model of bone marrow transplantation therapy against retroviral infection.来自Fv-4抗性供体的骨髓移植可使感染Friend白血病病毒的小鼠免于白血病:一种针对逆转录病毒感染的骨髓移植治疗模型。
Leukemia. 1994 Dec;8(12):2200-6.
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Secretion of a murine retroviral Env associated with resistance to infection.与抗感染抗性相关的鼠逆转录病毒Env的分泌。
J Gen Virol. 1997 Apr;78 ( Pt 4):785-93. doi: 10.1099/0022-1317-78-4-785.
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Resistance to Friend leukemia virus in transgenic mice expressing the native Fv-4 gene.表达天然Fv-4基因的转基因小鼠对Friend白血病病毒的抗性
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A gene therapy model for retrovirus-induced disease with a viral env gene: expression-dependent resistance in immunosuppressed hosts.一种具有病毒env基因的逆转录病毒诱导疾病的基因治疗模型:免疫抑制宿主中的表达依赖性抗性。
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Transgenic Fv-4 mice resistant to Friend virus.对Friend病毒有抗性的转基因Fv-4小鼠。
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Irradiation does not compromise or exacerbate the innate immune response in the brains of mice that were transplanted with bone marrow stem cells.对于移植了骨髓干细胞的小鼠大脑,辐射不会损害或加剧其先天免疫反应。
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Methotrexate preconditioning allows sufficient engraftment to confer drug resistance in mice transplanted with marrow expressing drug-resistant dihydrofolate reductase activity.甲氨蝶呤预处理可使移植了表达耐药二氢叶酸还原酶活性骨髓的小鼠实现足够的植入,从而赋予耐药性。
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The Ly-6A (Sca-1) GFP transgene is expressed in all adult mouse hematopoietic stem cells.Ly-6A(Sca-1)绿色荧光蛋白转基因在所有成年小鼠造血干细胞中表达。
Stem Cells. 2002;20(6):514-21. doi: 10.1634/stemcells.20-6-514.

引用本文的文献

1
Resistance to Friend murine leukemia virus infection conferred by the Fv-4 gene is recessive but appears dominant from the effect of the immune system.Fv-4基因赋予的对Friend小鼠白血病病毒感染的抗性是隐性的,但从免疫系统的效应来看似乎是显性的。
J Virol. 2000 Jul;74(13):6193-7. doi: 10.1128/jvi.74.13.6193-6197.2000.
2
Properties of the naturally occurring soluble surface glycoprotein of ecotropic murine leukemia virus: binding specificity and possible conformational change after binding to receptor.嗜亲性鼠白血病病毒天然存在的可溶性表面糖蛋白的特性:结合特异性以及与受体结合后的可能构象变化
J Virol. 2000 Feb;74(4):1815-26. doi: 10.1128/jvi.74.4.1815-1826.2000.
3
Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates.
旧世界灵长类动物中的人类内源性逆转录病毒K同源序列及其编码能力。
J Virol. 1998 Mar;72(3):1870-5. doi: 10.1128/JVI.72.3.1870-1875.1998.
4
Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection.携带Fv - 4基因的裸鼠对Friend鼠白血病病毒感染的易感性。
J Virol. 1997 Jan;71(1):750-4. doi: 10.1128/JVI.71.1.750-754.1997.
5
Murine leukemia virus envelope protein in transgenic-mouse serum blocks infection in vitro.转基因小鼠血清中的鼠白血病病毒包膜蛋白可在体外阻断感染。
J Virol. 1996 Mar;70(3):1882-9. doi: 10.1128/JVI.70.3.1882-1889.1996.