Role of the lipid rafts in the life cycle of canine coronavirus.
Role of the lipid rafts in the life cycle of canine coronavirus.
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DOI：
10.1099/vir.0.070870-0
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Colao V
中科院分区：
文献类型：
--
作者：
Pratelli A;Colao V
冠状病毒是一种有包膜的RNA病毒，与宿主细胞形成复杂的关系，并调节其脂质组成、脂质合成和信号传导。脂筏是一种特殊的质膜微区，富含鞘脂、胆固醇和相关蛋白，参与病毒感染的多种过程。胆固醇的提取导致脂质微区的解体和与脂筏结合的蛋白质的解离。由于富含胆固醇的微区似乎是非eneveloped病毒和几种冠状病毒的进入机制的一般特征，本研究的目的是分析脂质对犬冠状病毒（CCoV）感染性的贡献。CCoV的生命周期与质膜胆固醇密切相关，从细胞进入到病毒颗粒的产生。用甲基-β-环糊精（MβCD）去除胆固醇，破坏脂筏。细胞膜胆固醇的消耗导致病毒感染性的剂量依赖性降低，但不是消除，并且在15 mM的浓度下，感染率的降低约为68%。 MβCD处理用于验证包膜中的胆固醇是否是CCoV感染所必需的。这导致剂量依赖性抑制作用，在9 mM MβCD浓度下，感染性降低约73%。 由于病毒进入将构成抗病毒策略的靶标，与病毒和/或细胞膜相互作用或干扰脂质代谢的抑制性分子可能具有强的抗病毒潜力。这将是有趣的，在未来分析的CCoV包膜中的膜微区。
Coronaviruses are enveloped RNA viruses that have evolved complex relationships with their host cells, and modulate their lipid composition, lipid synthesis and signalling. Lipid rafts, enriched in sphingolipids, cholesterol and associated proteins, are special plasma membrane microdomains involved in several processes in viral infections. The extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to lipid rafts. Because cholesterol-rich microdomains appear to be a general feature of the entry mechanism of non-eneveloped viruses and of several coronaviruses, the purpose of this study was to analyse the contribution of lipids to the infectivity of canine coronavirus (CCoV). The CCoV life cycle is closely connected to plasma membrane cholesterol, from cell entry to viral particle production. The methyl-β-cyclodextrin (MβCD) was employed to remove cholesterol and to disrupt the lipid rafts. Cholesterol depletion from the cell membrane resulted in a dose-dependent reduction, but not abolishment, of virus infectivity, and at a concentration of 15 mM, the reduction in the infection rate was about 68 %. MβCD treatment was used to verify if cholesterol in the envelope was required for CCoV infection. This resulted in a dose-dependent inhibitory effect, and at a concentration of 9 mM MβCD, infectivity was reduced by about 73 %. Since viral entry would constitute a target for antiviral strategies, inhibitory molecules interacting with viral and/or cell membranes, or interfering with lipid metabolism, may have strong antiviral potential. It will be interesting in the future to analyse the membrane microdomains in the CCoV envelope.
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