CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China; CAS Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, 100101 Beijing, China.
Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871 Beijing, China.
Cell. 2019 May 30;177(6):1553-1565.e16. doi: 10.1016/j.cell.2019.04.035. Epub 2019 May 16.
Enterovirus B (EV-B), a major proportion of the genus Enterovirus in the family Picornaviridae, is the causative agent of severe human infectious diseases. Although cellular receptors for coxsackievirus B in EV-B have been identified, receptors mediating virus entry, especially the uncoating process of echovirus and other EV-B remain obscure. Here, we found that human neonatal Fc receptor (FcRn) is the uncoating receptor for major EV-B. FcRn binds to the virus particles in the "canyon" through its FCGRT subunit. By obtaining multiple cryo-electron microscopy structures at different stages of virus entry at atomic or near-atomic resolution, we deciphered the underlying mechanisms of enterovirus attachment and uncoating. These structures revealed that different from the attachment receptor CD55, binding of FcRn to the virions induces efficient release of "pocket factor" under acidic conditions and initiates the conformational changes in viral particle, providing a structural basis for understanding the mechanisms of enterovirus entry.
肠道病毒 B（EV-B）是小 RNA 病毒科肠道病毒属的主要成员之一，是引起严重人类传染病的病原体。虽然已经鉴定出 EV-B 中 Coxsackievirus B 的细胞受体，但介导病毒进入的受体，特别是肠道病毒和其他 EV-B 的脱壳过程仍不清楚。在这里，我们发现人类新生 Fc 受体（FcRn）是主要 EV-B 的脱壳受体。FcRn 通过其 FCGRT 亚基与“峡谷”中的病毒颗粒结合。通过获得不同阶段进入病毒的多个 cryo-EM 结构在原子或近原子分辨率下，我们破译了肠道病毒附着和脱壳的潜在机制。这些结构表明，与附着受体 CD55 不同，FcRn 与病毒颗粒的结合在酸性条件下有效地释放“口袋因子”，并启动病毒颗粒的构象变化，为理解肠道病毒进入的机制提供了结构基础。
