Human immunodeficiency virus type 1 (HIV-1) fusion with model membranes: kinetic analysis and the role of lipid composition, pH and divalent cations.
Human immunodeficiency virus type 1 (HIV-1) fusion with model membranes: kinetic analysis and the role of lipid composition, pH and divalent cations.
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人类免疫缺陷病毒 1 型 (HIV-1) 与模型膜融合：动力学分析以及脂质成分、pH 值和二价阳离子的作用。
DOI：
10.1016/0005-2736(93)90007-m
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Düzgüneş,N
中科院分区：
文献类型：
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作者：
Larsen,CE;Nir,S;Alford,DR;Jennings,M;Lee,KD;Düzgüneş,N
研究了HIV-1与模型膜融合的动力学和程度。用氯化十八烷基罗丹明B标记HIV-1，随着探针稀释到靶膜上，持续监测融合情况。用质量作用模型对结果进行了分析，该模型对荧光增强的动力学和最终程度进行了很好的模拟和预测。该模型确定了能够融合的病毒粒子的百分比以及融合、聚集和解离的速率常数。通过电镜对病毒和反应产物的超微结构分析也提供了HIV-1与缺乏CD4的膜融合的证据。HIV-1融合活性取决于靶膜脂组成的顺序：心磷脂(CL) > >磷脂酰肌醇> CL/二油基磷脂酰胆碱（DOPC）（3:7）、磷脂酸>磷脂酰丝氨酸（PS）、PS/胆固醇(2:1)> PS/PC（1:1）、PS/磷脂酰乙醇胺(1:1)> DOPC、红细胞鬼影。pH从7.5降低通常会提高HIV-1融合的速度和程度。生理上相关浓度的钙刺激HIV-1与几种脂质体组成和红细胞鬼影膜融合。HIV-1与脂质体的融合产物由单个病毒和多个脂质体组成。质量作用分析表明，与完整病毒粒子相比，融合产物的融合速率常数显著降低。与流感病毒和仙台病毒一样，HIV-1与含有自身包膜糖蛋白的膜的融合受到强烈抑制。与这些病毒不同，HIV-1的融合是由生理水平的钙促进的。HIV-1与脂质体的融合在性质上类似于猴免疫缺陷病毒的融合。
The kinetics and extent of HIV-1 fusion with model membranes was studied. HIV-1 was labeled with octadecyl rhodamine B chloride, and fusion was monitored continuously as the dilution of the probe into target membranes. The results were analyzed by a mass action model which yielded good simulations and predictions for the kinetics and final extents of fluorescence increase. The model determined the percents of virions capable of fusing and rate constants of fusion, aggregation and dissociation. Ultrastructural analysis of the virus and reaction products by electron microscopy also provided evidence of HIV-1 fusion with membranes lacking CD4. HIV-1 fusion activity depends on the target membrane lipid composition according to the sequence: cardiolipin (CL) > > phosphatidylinositol > CL/dioleoylphosphatidylcholine (DOPC) (3 : 7), phosphatidic acid > phosphatidylserine (PS), PS/cholesterol (2:1) > PS/PC (1:1), PS/phosphatidylethanolamine (1:1) > DOPC, erythrocyte ghosts. Reduction of pH from 7.5 generally enhances the rate and extent of HIV-1 fusion. Physiologically relevant concentrations of calcium stimulate HIV-1 fusion with several liposome compositions and with erythrocyte ghost membranes. The fusion products of HIV-1 with liposomes consist of a single virus and several liposomes. The mass action analysis revealed that, compared to intact virions, the fusion products show a striking reduction in the fusion rate constant. Like influenza and Sendai viruses, HIV-1 fusion with membranes containing its own envelope glycoprotein(s) is strongly inhibited. Unlike these viruses, HIV-1 fusion is promoted by physiological levels of calcium. HIV-1 fusion with liposomes is qualitatively similar to simian immunodeficiency virus fusion.