新型抗CD4单克隆抗体可将人类免疫缺陷病毒感染及CD4+细胞融合与病毒结合区分开来。
Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding.
作者信息
Healey D, Dianda L, Moore J P, McDougal J S, Moore M J, Estess P, Buck D, Kwong P D, Beverley P C, Sattentau Q J
机构信息
Academic Department of Genito-Urinary Medicine, University College and Middlesex School of Medicine, London.
出版信息
J Exp Med. 1990 Oct 1;172(4):1233-42. doi: 10.1084/jem.172.4.1233.
Abstract
Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.
摘要
人类免疫缺陷病毒（HIV）通过CD4与病毒包膜糖蛋白gp120之间的相互作用与细胞结合。先前的研究已将gp120的高亲和力结合位点定位到CD4的第一个结构域，与该区域反应的单克隆抗体（mAb）与gp120结合竞争，从而阻断病毒感染性和多核体形成。尽管对gp120与CD4的结合有详细了解，但对于导致膜融合和病毒进入的后续事件知之甚少。我们描述了两种与CD4的第三个结构域反应的新型单克隆抗体，它们抑制病毒结合后对HIV感染性和细胞融合至关重要的步骤。这些抗体不会抑制重组gp120或病毒与CD4的结合，然而，多种HIV分离株的感染和多核体形成受到阻断。这些发现表明，除了病毒结合外，CD4可能在膜融合中发挥积极作用。
相似文献
1
Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding.新型抗CD4单克隆抗体可将人类免疫缺陷病毒感染及CD4+细胞融合与病毒结合区分开来。
J Exp Med. 1990 Oct 1;172(4):1233-42. doi: 10.1084/jem.172.4.1233.
2
3
Synergistic inhibition of human immunodeficiency virus type 1 envelope glycoprotein-mediated cell fusion and infection by an antibody to CD4 domain 2 in combination with anti-gp120 antibodies.抗CD4结构域2抗体与抗gp120抗体联合对人免疫缺陷病毒1型包膜糖蛋白介导的细胞融合和感染的协同抑制作用
J Virol. 1995 Jul;69(7):4267-73. doi: 10.1128/JVI.69.7.4267-4273.1995.
4
5
A monoclonal antibody to the gp120-CD4 complex has differential effect on HIV-induced syncytium formation and viral infectivity.一种针对gp120-CD4复合物的单克隆抗体对HIV诱导的合胞体形成和病毒感染性具有不同的影响。
J Gen Virol. 1995 Mar;76 ( Pt 3):669-79. doi: 10.1099/0022-1317-76-3-669.
6
Enhancement of human immunodeficiency virus type 1 envelope-mediated fusion by a CD4-gp120 complex-specific monoclonal antibody.一种CD4-gp120复合物特异性单克隆抗体增强1型人类免疫缺陷病毒包膜介导的融合作用。
J Virol. 1997 Aug;71(8):6037-43. doi: 10.1128/JVI.71.8.6037-6043.1997.
7
Sequential CD4-coreceptor interactions in human immunodeficiency virus type 1 Env function: soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120.人类免疫缺陷病毒1型Env功能中的连续CD4共受体相互作用：可溶性CD4激活Env以实现共受体依赖性融合，并揭示抗体对gp120上隐蔽保守表位的阻断活性。
J Virol. 2000 Jan;74(1):326-33. doi: 10.1128/jvi.74.1.326-333.2000.
8
Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans.1型人类免疫缺陷病毒与HeLa CD4细胞的附着不依赖CD4，依赖gp120，且需要细胞表面的硫酸乙酰肝素。
J Virol. 1998 May;72(5):3623-34. doi: 10.1128/JVI.72.5.3623-3634.1998.
9
Binding of antibodies to virion-associated gp120 molecules of primary-like human immunodeficiency virus type 1 (HIV-1) isolates: effect on HIV-1 infection of macrophages and peripheral blood mononuclear cells.抗体与原发性人类免疫缺陷病毒1型（HIV-1）分离株的病毒体相关gp120分子的结合：对巨噬细胞和外周血单核细胞HIV-1感染的影响。
Virology. 1997 Mar 17;229(2):360-9. doi: 10.1006/viro.1997.8443.
10
引用本文的文献
1
Ion Binding Properties of a Naturally Occurring Metalloantibody.一种天然存在的金属抗体的离子结合特性。
Antibodies (Basel). 2020 Apr 16;9(2):10. doi: 10.3390/antib9020010.
2
Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity.发现并鉴定一种具有强效抗 HIV 活性的新型 CD4 结合连接子。
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00508-17. Print 2017 Aug.
3
A strategy to identify linker-based modules for the allosteric regulation of antibody-antigen binding affinities of different scFvs.一种用于识别基于接头的模块以对不同单链抗体片段（scFv）的抗体-抗原结合亲和力进行变构调节的策略。
MAbs. 2017 Apr;9(3):404-418. doi: 10.1080/19420862.2016.1277302.
4
Buffering deleterious polymorphisms in highly constrained parts of HIV-1 envelope by flexible regions.通过灵活区域缓冲HIV-1包膜高度受限部分中的有害多态性。
Retrovirology. 2016 Jul 30;13(1):50. doi: 10.1186/s12977-016-0285-6.
5
A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity.与马拉维若耐药相关的HIV-1 V3环中的单残基变化会损害CCR5结合亲和力，同时增加复制能力。
Retrovirology. 2015 Jun 18;12:50. doi: 10.1186/s12977-015-0177-1.
6
A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway.由替雷利珠单抗结合的特定CD4表位通过独特的信号通路介导调节性T细胞的激活。
Immunol Cell Biol. 2015 Apr;93(4):396-405. doi: 10.1038/icb.2014.102. Epub 2014 Dec 16.
7
Cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies.细胞间传播使 HIV-1 能够逃避强效 CD4bs 定向抗体的抑制。
PLoS Pathog. 2012;8(4):e1002634. doi: 10.1371/journal.ppat.1002634. Epub 2012 Apr 5.
8
CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells.CCR5 抗体 HGS004 和 HGS101 优先抑制药物结合的 CCR5 感染，并恢复原发性细胞中马拉维若耐药 HIV-1 的药物敏感性。
Virology. 2011 Mar 1;411(1):32-40. doi: 10.1016/j.virol.2010.12.029. Epub 2011 Jan 12.
9
Thermal stability of the human immunodeficiency virus type 1 (HIV-1) receptors, CD4 and CXCR4, reconstituted in proteoliposomes.人免疫缺陷病毒 1 型（HIV-1）受体 CD4 和 CXCR4 在脂蛋白体中重建的热稳定性。
PLoS One. 2010 Oct 13;5(10):e13249. doi: 10.1371/journal.pone.0013249.
10
Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition.病毒突触介导的人类免疫缺陷病毒 1 型在 T 细胞间的传播对进入抑制敏感。
J Virol. 2010 Apr;84(7):3516-27. doi: 10.1128/JVI.02651-09. Epub 2010 Jan 20.
本文引用的文献
1
Membrane fusion proteins of enveloped animal viruses.包膜动物病毒的膜融合蛋白。
Q Rev Biophys. 1983 May;16(2):151-95. doi: 10.1017/s0033583500005072.
2
The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.CD4（T4）抗原是艾滋病逆转录病毒受体的重要组成部分。
Nature. 1984;312(5996):763-7. doi: 10.1038/312763a0.
3
T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV.T淋巴细胞T4分子作为人类逆转录病毒LAV的受体。
Nature. 1984;312(5996):767-8. doi: 10.1038/312767a0.
4
Structure and expression of the human and mouse T4 genes.人类和小鼠T4基因的结构与表达
Proc Natl Acad Sci U S A. 1987 Dec;84(24):9155-9. doi: 10.1073/pnas.84.24.9155.
5
HIV infection does not require endocytosis of its receptor, CD4.HIV感染并不需要其受体CD4的内吞作用。
Cell. 1988 Sep 9;54(6):865-74. doi: 10.1016/s0092-8674(88)91241-x.
6
Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4.人类免疫缺陷病毒的内化不需要CD4的胞质结构域。
Nature. 1988 Jul 14;334(6178):162-5. doi: 10.1038/334162a0.
7
Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen.人类T细胞蛋白CD4与主要组织相容性复合体HLA-DR抗原之间的功能相互作用。
Nature. 1987;328(6131):626-9. doi: 10.1038/328626a0.
8
pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane.pH 非依赖性的 HIV 通过病毒包膜与质膜融合进入 CD4 阳性 T 细胞。
Cell. 1987 Jun 5;49(5):659-68. doi: 10.1016/0092-8674(87)90542-3.
9
Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains.大鼠CD4（W3/25）抗原的肽和核苷酸序列：源自具有四个免疫球蛋白相关结构域的结构的证据。
Proc Natl Acad Sci U S A. 1987 Mar;84(6):1649-53. doi: 10.1073/pnas.84.6.1649.
10
Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein.HTLV-III/LAV包膜糖蛋白诱导依赖CD4的细胞融合。
Nature. 1986;323(6090):725-8. doi: 10.1038/323725a0.
Zotero 插件