Cholesterol Supplementation During Production Increases the Infectivity of Retroviral and Lentiviral Vectors Pseudotyped with the Vesicular Stomatitis Virus Glycoprotein (VSV-G).
Cholesterol Supplementation During Production Increases the Infectivity of Retroviral and Lentiviral Vectors Pseudotyped with the Vesicular Stomatitis Virus Glycoprotein (VSV-G).
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DOI：
10.1016/j.bej.2008.12.004
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发表时间：
2009-05-15
影响因子：
3.9
通讯作者：
Miller WM
中科院分区：
文献类型：
--
作者：
Chen Y;Ott CJ;Townsend K;Subbaiah P;Aiyar A;Miller WM
胆固醇是质膜脂筏的主要成分，对包膜病毒（包括流感病毒和HIV-1）的组装和出芽非常重要。胆固醇耗竭损害病毒组装和感染性。本研究检查了外源性胆固醇添加（作为与甲基-β-环糊精（MbCD）的复合物递送）对Molony小鼠白血病病毒（MoMuLV）逆转录病毒载体和基于HIV-1的慢病毒载体（用水泡性口炎病毒糖蛋白（VSV-G）假型化）的影响。在载体生产之前和过程中补充胆固醇分别使逆转录病毒和慢病毒载体的感染性增强了4倍和6倍。相反，逆转录病毒载体的产生量不变，而慢病毒载体的产生量增加不到2倍。293-gag-pol生产细胞中的游离胆固醇和胆固醇酯含量均随胆固醇添加而增加。相比之下，磷脂头基组合物基本上没有变化的胆固醇补充293-gag-pol包装细胞。基于这些结果，提出胆固醇补充增加VSV-G假型逆转录病毒和慢病毒载体的感染性，可能通过改变病毒载体组装和出芽的生产细胞膜的组成，和/或通过改变病毒载体的脂质组成。
Cholesterol, a major component of plasma membrane lipid rafts, is important for assembly and budding of enveloped viruses, including influenza and HIV-1. Cholesterol depletion impairs virus assembly and infectivity. This study examined the effects of exogenous cholesterol addition (delivered as a complex with methyl-beta-cyclodextrin (MbCD)) on the production of Molony murine leukemia virus (MoMuLV) retroviral vector and HIV-1-based lentiviral vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Cholesterol supplementation before and during vector production enhanced the infectivity of retroviral and lentiviral vectors up to 4-fold and 6-fold, respectively. In contrast, the amount of retroviral vector produced was unchanged, and that of lentiviral vector was increased less than 2-fold. Both free cholesterol and cholesterol ester content in 293-gag-pol producer cells increased with cholesterol addition. In contrast, the phospholipids headgroup composition was essentially unchanged by cholesterol supplementation in 293-gag-pol packaging cells. Based on these results, it is proposed that cholesterol supplementation increases the infectivity of VSV-G-pseudotyped retroviral and lentiviral vectors, possibly by altering the composition of the producer cell membrane where the viral vectors are assembled and bud, and/or by changing the lipid composition of the viral vectors.
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影响因子：
3.7
作者：
Ono, Akira;Waheed, Abdul A.;Freed, Eric O.
通讯作者：
Freed, Eric O.
DOI：
10.1083/jcb.140.6.1357
发表时间：
1998-03-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Keller P;Simons K
通讯作者：
Simons K
影响因子：
7.8
作者：
Prior, Ian A;Muncke, Cornelia;Parton, Robert G;Hancock, John F
通讯作者：
Hancock, John F
影响因子：
5.4
作者：
Lindwasser, OW;Resh, MD
通讯作者：
Resh, MD
影响因子：
2.9
作者：
Chen, Y;Miller, WM;Aiyar, A
通讯作者：
Aiyar, A