Methyl-β-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts
Methyl-β-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts
复制标题
甲基-β-环糊精通过干扰脂筏中病毒颗粒和 ICAM-5 的积累来抑制 EV-D68 病毒进入
DOI：
10.1016/j.antiviral.2020.104752
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发表时间：
2020-04-01
影响因子：
7.6
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Jiang, Yunhe;Liu, Shunan;Wei, Wei
肠道病毒D 68（EV-D 68）是小核糖核酸病毒家族的成员，是儿童呼吸道疾病的病原体。近年来，EV-D 68感染的发病率在全球范围内增加。到目前为止，还没有针对EV-D 68的批准的抗病毒剂或疫苗。在这里，我们表明甲基-β-环糊精（M β CD）是一种破坏脂筏的常见药物，可以特异性抑制EV-D 68感染，在杀病毒浓度下不会产生显着的细胞毒性。外源性胆固醇的加入减弱了M β CD的抗EV-D 68活性。M β CD处理对病毒颗粒附着于细胞膜的影响很弱，但显著抑制EV-D 68进入宿主细胞。我们证明了EV-D 68促进了病毒受体ICAM-5易位到感染细胞的膜筏上。用M β CD处理后，细胞中病毒颗粒与ICAM-5在脂筏中的共定位被彻底消除。最后，我们发现M β CD抑制了分离的循环EV-D 68菌株的复制。总之，我们的研究结果表明，M β CD通过干扰病毒颗粒和ICAM-5在脂筏中的积累来抑制EV-D 68复制。这种机制代表了药物开发的一种有前途的策略。
Enterovirus D68 (EV-D68) is a member of the Picornavirus family and a causative agent of respiratory diseases in children. The incidence of EV-D68 infection has increased worldwide in recent years. Thus far, there are no approved antiviral agents or vaccines for EV-D68. Here, we show that methyl-beta-cyclodextrin (M beta CD), a common drug that disrupts lipid rafts, specifically inhibits EV-D68 infection without producing significant cytotoxicity at virucidal concentrations. The addition of exogenous cholesterol attenuated the anti-EV-D68 activity of M beta CD. M beta CD treatment had a weak influence on the attachment of viral particles to the cell membrane but significantly inhibited EV-D68 entry into host cells. We demonstrated that EV-D68 facilitated the translocation of the viral receptor ICAM-5 to membrane rafts in infected cells. The colocalization of viral particles with ICAM-5 in lipid rafts was thoroughly abolished in cells after treatment with M beta CD. Finally, we showed that M beta CD inhibited the replication of isolated circulating EV-D68 strains. In summary, our results demonstrate that M beta CD suppresses EV-D68 replication by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts. This mechanism represents a promising strategy for drug development.