Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B

• Published in: Cell Vol. 177; no. 6; pp. 1553 - 1565.e16
• Main Authors: Zhao, Xin, Zhang, Guigen, Liu, Sheng, Chen, Xiangpeng, Peng, Ruchao, Dai, Lianpan, Qu, Xiao, Li, Shihua, Song, Hao, Gao, Zhengrong, Yuan, Pengfei, Liu, Zhiheng, Li, Changyao, Shang, Zifang, Li, Yan, Zhang, Meifan, Qi, Jianxun, Wang, Han, Du, Ning, Wu, Yan, Bi, Yuhai, Gao, Shan, Shi, Yi, Yan, Jinghua, Zhang, Yong, Xie, Zhengde, Wei, Wensheng, Gao, George F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2019
• Subjects: attachment; Capsid - metabolism; cryo-electron microscopy; cryo-EM; Cryoelectron Microscopy; echovirus; Enterovirus; Enterovirus B; Enterovirus B, Human - metabolism; Enterovirus B, Human - pathogenicity; Enterovirus Infections - metabolism; etiological agents; FcRn; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class I - physiology; Histocompatibility Antigens Class I - ultrastructure; human neonatal Fc receptor; Humans; infectious diseases; Models, Molecular; Phylogeny; receptor; receptors; Receptors, Fc - metabolism; Receptors, Fc - physiology; Receptors, Fc - ultrastructure; uncoating; Virion; Virus Internalization; viruses; uncoating; receptor; enterovirus; attachment; FcRn; human neonatal Fc receptor; cryo-EM; echovirus
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2019.04.035

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. [Display omitted] •CRISPR screening identified FcRn as an essential and universal EV-B receptor•FcRn facilitates EV-B uncoating and CD55 for attachment•High-resolution Cryo-EM structures described the mechanism of virus entry•The molecular mechanism of dual (attachment versus uncoating) receptor-usage was illustrated The human neonatal Fc receptor is the uncoating receptor that facilitates cellular viral entry for Enteroviruses, such as echovirus.