Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China; Department of Pathogenobiology, College of Basic Medical Science, Jilin University, Changchun, Jilin, 130021, China.
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
Antiviral Res. 2020 Apr;176:104752. doi: 10.1016/j.antiviral.2020.104752. Epub 2020 Feb 23.
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-β-cyclodextrin (MβCD), 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 MβCD. MβCD 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 MβCD. Finally, we showed that MβCD inhibited the replication of isolated circulating EV-D68 strains. In summary, our results demonstrate that MβCD 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.
肠道病毒 D68（EV-D68）属于小 RNA 病毒科，是引起儿童呼吸道疾病的病原体之一。近年来，EV-D68 在全球的发病率呈上升趋势。目前，尚无针对 EV-D68 的批准抗病毒药物或疫苗。本研究表明，甲基-β-环糊精（MβCD）是一种破坏脂筏的常用药物，可在不产生明显细胞毒性的病毒杀伤浓度下，特异性抑制 EV-D68 感染。外源性胆固醇的添加可减弱 MβCD 对 EV-D68 的抑制作用。MβCD 处理对病毒颗粒与细胞膜的附着几乎没有影响，但可显著抑制 EV-D68 进入宿主细胞。我们证实 EV-D68 可促进病毒受体 ICAM-5 在感染细胞中的质膜筏内易位。在用 MβCD 处理后，病毒颗粒与 ICAM-5 在质膜筏中的共定位完全被消除。最后，我们发现 MβCD 可抑制分离的循环 EV-D68 株的复制。综上所述，我们的研究结果表明，MβCD 通过干扰病毒颗粒和 ICAM-5 在脂筏中的聚集来抑制 EV-D68 的复制。该机制为药物开发提供了一种有前景的策略。
