Desmosterol Increases Lipid Bilayer Fluidity during Hepatitis C Virus Infection.
Desmosterol Increases Lipid Bilayer Fluidity during Hepatitis C Virus Infection.
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DOI：
10.1021/acsinfecdis.6b00086
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发表时间：
2016-11-11
影响因子：
5.3
通讯作者：
Yang, Priscilla L.
中科院分区：
文献类型：
--
作者：
Costello, Deirdre A.;Villareal, Valerie A.;Yang, Priscilla L.
关键词：
丙型肝炎病毒（HCV）通过增加细胞内二氢胆固醇的含量并影响其定位，独特地影响二氢胆固醇的稳态。这些作用对病毒的有效复制很重要，因为抑制二氢胆固醇的合成具有抗病毒作用，而添加外源性二氢胆固醇可挽救这种作用。在此，我们利用亚基因组复制子表明二氢胆固醇对HCV JFH1 RNA的复制有重要影响。利用合成的支撑脂质双层进行的光漂白后荧光恢复（FRAP）实验表明，用二氢胆固醇替代胆固醇可显著增加脂质双层的流动性，尤其是在存在饱和磷脂和神经酰胺的情况下。我们利用液相色谱 - 质谱（LC - MS）证明，在发生基因组复制的膜中二氢胆固醇含量丰富，并且与从无HCV的细胞中分离的阴性对照膜相比，源自这些特殊膜的支撑脂质双层也表现出显著更高的流动性。总之，这些数据表明了一个模型，即二氢胆固醇对脂质双层的促流动性作用在HCV感染期间内质网发生的广泛膜重塑中起关键作用。我们预计所描述的支撑脂质双层系统可提供一个有用的模型系统，用于探究脂质结构和组成对脂质膜生物物理特性及其在病毒过程（如基因组复制）中的功能的影响。
Hepatitis C virus (HCV) uniquely affects desmosterol homeostasis by increasing its intracellular abundance and affecting its localization. These effects are important for productive viral replication since inhibition of desmosterol synthesis has an antiviral effect that can be rescued by the addition of exogenous desmosterol. Here, we use subgenomic replicons to show that desmosterol has a major effect on replication of HCV JFH1 RNA. Fluorescence recovery after photobleaching (FRAP) experiments performed with synthetic supported lipid bilayers demonstrate that substitution of desmosterol for cholesterol significantly increases lipid bilayer fluidity, especially in the presence of saturated phospholipids and ceramides. We demonstrate using LC-MS that desmosterol is abundant in the membranes upon which genome replication takes place and that supported lipid bilayers derived from these specialized membranes also exhibit significantly higher fluidity compared to negative control membranes isolated from cells lacking HCV. Together, these data suggest a model in which the fluidity-promoting effects of desmosterol on lipid bilayers play a crucial role in the extensive membrane remodeling that takes place in the endoplasmic reticulum during HCV infection. We anticipate that the supported lipid bilayer system described can provide a useful model system in which to interrogate the effects of lipid structure and composition on the biophysical properties of lipid membranes as well as their function in viral processes such as genome replication.
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影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
DOI：
10.1016/s1388-1981(00)00084-6
发表时间：
2000-08-24
影响因子：
4.8
作者：
Borst, JW;Visser, NV;Visser, AJWG
通讯作者：
Visser, AJWG
影响因子：
3.9
作者：
Costello, Deirdre A.;Hsia, Chih-Yun;Daniel, Susan
通讯作者：
Daniel, Susan
影响因子：
5.4
作者：
Kapadia, Sharookh B.;Barth, Heidi;Chisari, Francis V.
通讯作者：
Chisari, Francis V.
影响因子：
4.9
作者：
Chamoun-Emanuelli, Ana M.;Pecheur, Eve-Isabelle;Chen, Zhilei
通讯作者：
Chen, Zhilei