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可溶性CD4蛋白可选择性抑制HIV复制及合胞体形成。

A soluble CD4 protein selectively inhibits HIV replication and syncytium formation.

作者信息

Hussey R E, Richardson N E, Kowalski M, Brown N R, Chang H C, Siliciano R F, Dorfman T, Walker B, Sodroski J, Reinherz E L

机构信息

Laboratories of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

出版信息

Nature. 1988 Jan 7;331(6151):78-81. doi: 10.1038/331078a0.

DOI:10.1038/331078a0
PMID:2829023
Abstract

The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1-3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4-9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.

摘要

CD4(T4)分子在参与II类主要组织相容性复合体(MHC)识别的一部分T淋巴细胞上表达,并且可能是II类MHC一个或多个单态区域的生理受体(参考文献1 - 3)。CD4还作为人类免疫缺陷病毒(HIV)外膜糖蛋白(gp120)的受体发挥作用(参考文献4 - 9),这对于病毒进入宿主细胞和膜融合至关重要,而膜融合有助于病毒的细胞间传播及其细胞病变效应。我们利用杆状病毒表达系统制备了毫克量的CD4亲水性细胞外片段。纳摩尔浓度范围的可溶性CD4,如同某些抗CD4单克隆抗体一样,通过结合表达gp120的细胞来抑制合胞体形成和HIV感染。也许更重要的是,可溶性CD4蛋白不会抑制II类特异性T细胞相互作用,而等量的抗T4抗体实际上会消除这种相互作用。这可能反映出CD4对gp120和II类MHC的亲和力存在显著差异。

相似文献

1
A soluble CD4 protein selectively inhibits HIV replication and syncytium formation.可溶性CD4蛋白可选择性抑制HIV复制及合胞体形成。
Nature. 1988 Jan 7;331(6151):78-81. doi: 10.1038/331078a0.
2
HIV infection is blocked in vitro by recombinant soluble CD4.在体外,重组可溶性CD4可阻断HIV感染。
Nature. 1988 Jan 7;331(6151):76-8. doi: 10.1038/331076a0.
3
Soluble CD4 molecules neutralize human immunodeficiency virus type 1.可溶性CD4分子可中和1型人类免疫缺陷病毒。
Nature. 1988 Jan 7;331(6151):84-6. doi: 10.1038/331084a0.
4
A soluble form of CD4 (T4) protein inhibits AIDS virus infection.可溶性形式的CD4(T4)蛋白可抑制艾滋病病毒感染。
Nature. 1988 Jan 7;331(6151):82-4. doi: 10.1038/331082a0.
5
Receptor molecule blocks HIV.受体分子可阻断艾滋病毒。
Nature. 1988 Jan 7;331(6151):15. doi: 10.1038/331015a0.
6
Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding.鉴定影响II类主要组织相容性复合体与HIV-1 gp120结合的人CD4残基。
Nature. 1989 Jun 15;339(6225):548-51. doi: 10.1038/339548a0.
7
HLA-DR is involved in the HIV-1 binding site on cells expressing MHC class II antigens.HLA-DR参与表达MHC II类抗原的细胞上的HIV-1结合位点。
J Immunol. 1988 Aug 15;141(4):1131-6.
8
Fusion of human B cell lines with HIV-1 envelope-expressing T cells is enhanced by antigen-specific Ig receptors. Possible mechanism for elimination of gp120-specific B cells in vivo.抗原特异性Ig受体可增强人B细胞系与表达HIV-1包膜的T细胞的融合。体内消除gp120特异性B细胞的可能机制。
J Immunol. 1993 Mar 15;150(6):2506-16.
9
Characterization of CD4 glycoprotein determinant-HIV envelope protein interactions: perspectives for analog and vaccine development.CD4糖蛋白决定簇与HIV包膜蛋白相互作用的表征:类似物及疫苗开发前景
Crit Rev Immunol. 1988;8(4):315-39.
10
The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4.人类免疫缺陷病毒的包膜糖蛋白与CD4的免疫球蛋白样结构域结合。
Nature. 1988 Jul 14;334(6178):159-62. doi: 10.1038/334159a0.

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