膜筏微结构域介导HIV-1感染所需的侧向组装。
Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection.
作者信息
Mañes S, del Real G, Lacalle R A, Lucas P, Gómez-Moutón C, Sánchez-Palomino S, Delgado R, Alcamí J, Mira E, Martínez-A C
机构信息
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
出版信息
EMBO Rep. 2000 Aug;1(2):190-6. doi: 10.1093/embo-reports/kvd025.
Abstract
HIV-1 infection triggers lateral membrane diffusion following interaction of the viral envelope with cell surface receptors. We show that these membrane changes are necessary for infection, as initial gp120-CD4 engagement leads to redistribution and clustering of membrane microdomains, enabling subsequent interaction of this complex with HIV-1 co-receptors. Disruption of cell membrane rafts by cholesterol depletion before viral exposure inhibits entry by both X4 and R5 strains of HIV-1, although viral replication in infected cells is unaffected by this treatment. This inhibitory effect is fully reversed by cholesterol replenishment of the cell membrane. These results indicate a general mechanism for HIV-1 envelope glycoprotein-mediated fusion by reorganization of membrane microdomains in the target cell, and offer new strategies for preventing HIV-1 infection.
摘要
HIV-1感染在病毒包膜与细胞表面受体相互作用后引发细胞膜侧向扩散。我们发现这些膜变化对于感染是必要的，因为最初的gp120-CD4结合会导致膜微结构域的重新分布和聚集，从而使该复合物随后能够与HIV-1共受体相互作用。在病毒暴露前通过胆固醇耗竭破坏细胞膜脂筏会抑制HIV-1的X4和R5毒株的进入，尽管这种处理对感染细胞中的病毒复制没有影响。通过补充细胞膜胆固醇可完全逆转这种抑制作用。这些结果表明了一种由HIV-1包膜糖蛋白介导的、通过靶细胞膜微结构域重组实现融合的普遍机制，并为预防HIV-1感染提供了新策略。
相似文献
1
Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection.膜筏微结构域介导HIV-1感染所需的侧向组装。
EMBO Rep. 2000 Aug;1(2):190-6. doi: 10.1093/embo-reports/kvd025.
2
Human immunodeficiency virus type 1 uses lipid raft-colocalized CD4 and chemokine receptors for productive entry into CD4(+) T cells.1型人类免疫缺陷病毒利用脂筏共定位的CD4和趋化因子受体有效进入CD4(+) T细胞。
J Virol. 2002 May;76(10):4709-22. doi: 10.1128/jvi.76.10.4709-4722.2002.
3
Segregation of CD4 and CXCR4 into distinct lipid microdomains in T lymphocytes suggests a mechanism for membrane destabilization by human immunodeficiency virus.CD4和CXCR4在T淋巴细胞中分隔到不同的脂质微区，提示了一种人类免疫缺陷病毒导致膜不稳定的机制。
J Virol. 2002 Feb;76(4):1802-15. doi: 10.1128/jvi.76.4.1802-1815.2002.
4
Raft localization of CXCR4 is primarily required for X4-tropic human immunodeficiency virus type 1 infection.CXCR4的筏定位主要是X4嗜性1型人类免疫缺陷病毒感染所必需的。
Virology. 2009 Mar 30;386(1):23-31. doi: 10.1016/j.virol.2008.12.033.
5
Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1.脂筏与HIV发病机制：宿主细胞膜胆固醇是1型HIV感染所必需的。
AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1009-19. doi: 10.1089/088922201300343690.
6
Moesin is required for HIV-1-induced CD4-CXCR4 interaction, F-actin redistribution, membrane fusion and viral infection in lymphocytes.肌动蛋白结合蛋白（Moesin）是HIV-1诱导淋巴细胞中CD4与CXCR4相互作用、F-肌动蛋白重新分布、膜融合及病毒感染所必需的。
J Cell Sci. 2009 Jan 1;122(Pt 1):103-13. doi: 10.1242/jcs.035873. Epub 2008 Dec 9.
7
Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry.硫醇/二硫键交换是病毒进入过程中CXCR4嗜性HIV-1包膜介导的T细胞融合的前提条件。
Blood. 2004 Mar 1;103(5):1586-94. doi: 10.1182/blood-2003-05-1390. Epub 2003 Oct 30.
8
Use of a gp120 binding assay to dissect the requirements and kinetics of human immunodeficiency virus fusion events.使用gp120结合试验剖析人类免疫缺陷病毒融合事件的要求和动力学。
J Virol. 1999 Dec;73(12):10346-58. doi: 10.1128/JVI.73.12.10346-10358.1999.
9
Identification of determinants on a dualtropic human immunodeficiency virus type 1 envelope glycoprotein that confer usage of CXCR4.鉴定1型双嗜性人类免疫缺陷病毒包膜糖蛋白上决定使用CXCR4的决定簇。
J Virol. 1998 Mar;72(3):2509-15. doi: 10.1128/JVI.72.3.2509-2515.1998.
10
Blocking of HIV-1 infection by targeting CD4 to nonraft membrane domains.通过将CD4靶向非脂筏膜结构域来阻断HIV-1感染。
J Exp Med. 2002 Aug 5;196(3):293-301. doi: 10.1084/jem.20020308.
引用本文的文献
1
Revisiting Pathogen Exploitation of Clathrin-Independent Endocytosis: Mechanisms and Implications.重新审视病原体对网格蛋白非依赖性内吞作用的利用：机制与影响
Cells. 2025 May 16;14(10):731. doi: 10.3390/cells14100731.
2
An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.蛋白激酶作为治疗靶点的最新研究进展——第一部分：蛋白激酶 C 的激活及其在癌症和心血管疾病中的作用。
Int J Mol Sci. 2023 Dec 18;24(24):17600. doi: 10.3390/ijms242417600.
3
Pseudorabies virus upregulates low-density lipoprotein receptors to facilitate viral entry.伪狂犬病毒上调低密度脂蛋白受体以促进病毒进入。
J Virol. 2024 Jan 23;98(1):e0166423. doi: 10.1128/jvi.01664-23. Epub 2023 Dec 6.
4
Host Membranes as Drivers of Virus Evolution.宿主膜作为病毒进化的驱动力。
Viruses. 2023 Aug 31;15(9):1854. doi: 10.3390/v15091854.
5
Cholesterol-Lowering Drugs as Potential Antivirals: A Repurposing Approach against Flavivirus Infections.降脂药物作为潜在的抗病毒药物：针对黄病毒感染的再利用方法。
Viruses. 2023 Jun 28;15(7):1465. doi: 10.3390/v15071465.
6
Neutral sphingomyelinase 2 is required for HIV-1 maturation.中性鞘磷脂酶 2 是 HIV-1 成熟所必需的。
Proc Natl Acad Sci U S A. 2023 Jul 11;120(28):e2219475120. doi: 10.1073/pnas.2219475120. Epub 2023 Jul 5.
7
Electrostatic Surface Potential as a Key Parameter in Virus Transmission and Evolution: How to Manage Future Virus Pandemics in the Post-COVID-19 Era.静电表面电势作为病毒传播和进化的关键参数：在后 COVID-19 时代如何管理未来的病毒大流行。
Viruses. 2023 Jan 19;15(2):284. doi: 10.3390/v15020284.
8
Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future.SARS-CoV-2 和 HIV 表面包膜糖蛋白的趋同进化动力学受宿主细胞表面受体和脂筏驱动：对未来的启示。
Int J Mol Sci. 2023 Jan 18;24(3):1923. doi: 10.3390/ijms24031923.
9
Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?环糊精：仅仅是药用辅料还是成熟的候选药物？
Pharmaceutics. 2022 Nov 22;14(12):2559. doi: 10.3390/pharmaceutics14122559.
10
The host cytoskeleton: a key regulator of early HIV-1 infection.宿主细胞骨架：HIV-1 早期感染的关键调节因子。
FEBS J. 2024 May;291(9):1835-1848. doi: 10.1111/febs.16706. Epub 2022 Dec 26.
本文引用的文献
1
Glycosphingolipids promote entry of a broad range of human immunodeficiency virus type 1 isolates into cell lines expressing CD4, CXCR4, and/or CCR5.糖鞘脂促进多种1型人类免疫缺陷病毒分离株进入表达CD4、CXCR4和/或CCR5的细胞系。
J Virol. 2000 Jul;74(14):6377-85. doi: 10.1128/jvi.74.14.6377-6385.2000.
2
Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts.1型人类免疫缺陷病毒从富含糖脂的膜脂筏中选择性出芽的证据。
J Virol. 2000 Apr;74(7):3264-72. doi: 10.1128/jvi.74.7.3264-3272.2000.
3
Effects of the human CD38 glycoprotein on the early stages of the HIV-1 replication cycle.人类CD38糖蛋白对HIV-1复制周期早期阶段的影响。
FASEB J. 1999 Dec;13(15):2265-76. doi: 10.1096/fasebj.13.15.2265.
4
Membrane raft microdomains mediate front-rear polarity in migrating cells.膜筏微结构域介导迁移细胞的前后极性。
EMBO J. 1999 Nov 15;18(22):6211-20. doi: 10.1093/emboj/18.22.6211.
5
Constitutive cell surface association between CD4 and CCR5.CD4与CCR5之间的组成型细胞表面关联。
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7496-501. doi: 10.1073/pnas.96.13.7496.
6
Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency virus type 1 (HIV-1) entry: evidence for CD4-induced interactions between HIV-1 gp120 and reconstituted membrane microdomains of glycosphingolipids (Gb3 and GM3).人类红细胞糖鞘脂作为1型人类免疫缺陷病毒（HIV-1）进入细胞的替代辅助因子：CD4诱导HIV-1 gp120与重组糖鞘脂膜微结构域（Gb3和GM3）之间相互作用的证据。
J Virol. 1999 Jun;73(6):5244-8. doi: 10.1128/JVI.73.6.5244-5248.1999.
7
Maturation of the axonal plasma membrane requires upregulation of sphingomyelin synthesis and formation of protein-lipid complexes.轴突质膜的成熟需要鞘磷脂合成的上调和蛋白质-脂质复合物的形成。
EMBO J. 1999 Apr 1;18(7):1761-71. doi: 10.1093/emboj/18.7.1761.
8
Generation of retroviral vector for clinical studies using transient transfection.利用瞬时转染生成用于临床研究的逆转录病毒载体。
Hum Gene Ther. 1999 Jan 1;10(1):123-32. doi: 10.1089/10430349950019255.
9
T lymphocyte costimulation mediated by reorganization of membrane microdomains.由膜微区重组介导的T淋巴细胞共刺激。
Science. 1999 Jan 29;283(5402):680-2. doi: 10.1126/science.283.5402.680.
10
Functions of lipid rafts in biological membranes.生物膜中脂筏的功能。
Annu Rev Cell Dev Biol. 1998;14:111-36. doi: 10.1146/annurev.cellbio.14.1.111.
Zotero 插件