Effect of 25-hydroxycholesterol in viral membrane fusion: Insights on HIV inhibition
Effect of 25-hydroxycholesterol in viral membrane fusion: Insights on HIV inhibition
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DOI：
10.1016/j.bbamem.2018.02.001
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发表时间：
2018-05-01
影响因子：
3.4
通讯作者：
Santos, Nuno C.
中科院分区：
文献类型：
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作者：
Gomes, Barbara;Goncalves, Sonia;Santos, Nuno C.
最近发现，25-羟基胆固醇(25HC)是一种氧化的胆固醇衍生物，可抑制人类免疫缺陷病毒1型(HIV)进入其靶细胞。然而，参与这一行动的机制尚未建立。本工作的目的是研究25HC在生物膜模型系统中的作用以及在HIV-FP水平上的作用。在HIV融合过程中整合了不同的生物物理方法，以阐明由于25HC的存在而导致的膜水平的变化，从而抑制病毒感染。在表面压力研究中，模拟哺乳动物和HIV膜的脂泡被用于光谱分析和脂单分子膜。用F8rster共振能量转移法进行多肽诱导的脂质混合实验，计算融合效率。与胆固醇相比，在25HC存在的情况下，脂质体融合减少了50%。HIV-FP的构象通过红外线分析进行评估，它依赖于甾醇的性质。各向异性、表面压力和偶极电势分析表明，25HC中胆固醇的转化导致膜上胆固醇调节作用的丧失。通过不同的生物物理技术，我们表明25HC通过改变脂膜性质和直接改变HIV-FP结构来影响膜融合过程。目前的数据支持25HC具有广泛的抗病毒活性。
Recently, it was demonstrated that 25-hydroxycholesterol (25HC), an oxidized cholesterol derivative, inhibits human immunodeficiency virus type 1 (HIV) entry into its target cells. However, the mechanisms involved in this action have not yet been established. The aim of this work was to study the effects of 25HC in biomembrane model systems and at the level of HIV fusion peptide (HIV-FP). Integration of different biophysical approaches was made in the context of HIV fusion process, to clarify the changes at membrane level due to the presence of 25HC that result in the suppressing of viral infection.Lipid vesicles mimicking mammalian and HIV membranes were used on spectroscopy assays and lipid monolayers in surface pressure studies. Peptide-induced lipid mixing assays were performed by F8rster resonance energy transfer to calculate fusion efficiency. Liposome fusion is reduced by 50% in the presence of 25HC, comparatively to cholesterol. HIV-FP conformation was assessed by infrared assays and it relies on sterol nature. Anisotropy, surface pressure and dipole potential assays indicate that the conversion of cholesterol in 25HC leads to a loss of the cholesterol modulating effect on the membrane.With different biophysical techniques, we show that 25HC affects the membrane fusion process through the modification of lipid membrane properties, and by direct alterations on HIV-FP structure. The present data support a broad antiviral activity for 25HC.