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TitleHuman FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18.
Journal, issue, pagesmBio, Vol. 13, Issue 4, Page e0116622, Year 2022
Publish dateAug 30, 2022
AuthorsXiangpeng Chen / Xiao Qu / Congcong Liu / Yong Zhang / Guigen Zhang / Pu Han / Yali Duan / Qi Li / Liang Wang / Wenjing Ruan / Peiyi Wang / Wensheng Wei / George F Gao / Xin Zhao / Zhengde Xie /
PubMed AbstractVirus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus- ...Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus-related enterovirus species B serotypes in our previous study. Echovirus 18 (E18), as a member of enterovirus species B, is a significant causative agent of aseptic meningitis and viral encephalitis in children. However, it does not use CD55 as a critical host factor. We conducted CRISPR/Cas9 knockout screening to determine the receptors and entry mechanisms and identified FcRn working as a dual-function receptor for E18. Knockout of and , which encode the two subunits of FcRn, prevented infection by E18 and other echoviruses in the same physiological cluster. We then elucidated the underlying molecular mechanism of receptor recognition by E18 using cryogenic electron microscopy. The binding of the FCGRT subunit to the canyon region rotates the residues around the pocket, triggering the release of the pocket factor as observed for other enterovirus species B members. E18 is a member of enterovirus species B. As one of the most common enterovirus serotypes in nonpolio enterovirus detection, it easily infects children and causes various clinical symptoms. Aseptic meningitis and viral encephalitis are the most commonly reported syndromes associated with E18. No effective antiviral drugs or approved vaccines are available. Previous studies showed that CD55 and FcRn were the binding and uncoating receptors for some echoviruses. However, we found that CD55 is not the critical host factor for E18. Thus, we want to determine the receptors and elucidate the entry mechanism of E18. Our findings reveal that FcRn is a two-in-one attachment-uncoating receptor for E18.
External linksmBio / PubMed:35862785 / PubMed Central
MethodsEM (single particle)
Resolution3.09 - 3.37 Å
Structure data

EMDB-33499, PDB-7xxa:
Complex of Echo 18 and FcRn at pH7.4
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-33502, PDB-7xxg:
Echo 18 at pH5.5
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-33505, PDB-7xxj:
Echo 18 incubated with FcRn at pH5.5
Method: EM (single particle) / Resolution: 3.33 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • echovirus e18
  • homo sapiens (human)
KeywordsVIRUS / Complex / Receptor / Echo 18 / pH5.5 / RcRn

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