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Cell. 2019 May 30;177(6):1553-1565.e16. doi: 10.1016/j.cell.2019.04.035. Epub 2019 May 16.

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

Author information

1
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.
2
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.
3
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China; School of Life Sciences, University of Science and Technology of China, Hefei, 230026 Anhui, China.
4
Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Virology Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045 Beijing, China.
5
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
6
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, 100101 Beijing, China.
7
KunMing Institute of Zoology, Chinese Academy of Sciences, 650223 KunMing, China.
8
EdiGene Inc, Life Science Park, 22 KeXueYuan Road, Changping District, 102206 Beijing, China.
9
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; Academy for Advanced Interdisciplinary Studies, Peking University, 100871 Beijing, China.
10
CAS Key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, 215163 Suzhou, China.
11
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; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
12
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), 102206 Beijing, China; WHO WPRO Regional Polio Reference Laboratory, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 102206 Beijing, China.
13
Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Virology Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045 Beijing, China. Electronic address: xiezhengde@bch.com.cn.
14
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. Electronic address: wswei@pku.edu.cn.
15
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; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, 100101 Beijing, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), 102206 Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, 100049 Beijing, China. Electronic address: gaof@im.ac.cn.

Abstract

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.

KEYWORDS:

FcRn; attachment; cryo-EM; echovirus; enterovirus; human neonatal Fc receptor; receptor; uncoating

PMID:
31104841
DOI:
10.1016/j.cell.2019.04.035

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