Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18

Chen, Xiangpeng1; Qu, Xiao2; Liu, Congcong3,4; Zhang, Yong5,6; Zhang, Guigen7; Han, Pu2; Duan, Yali1; Li, Qi1; Wang, Liang2; Ruan, Wenjing2,8; Wang, Peiyi4; Wei, Wensheng9; Gao, George F.2; Zhao, Xin2,10; Xie, Zhengde1

2022-07-01

10.1128/mbio.01166-22

mBio   Impact Factor & Quartile

2150-7511

["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 FCGRT and B2M, 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. IMPORTANCE 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.","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."]

CRISPR Cas9 FcRn echovirus enterovirus receptors

SCI

English

Others

National Natural Science Foundation of China (NSFC)["81971922","82172245"] ; NSFC["82072289","32000127"] ; Beijing Nova Program of Science and Technology[Z191100001119030] ; Youth Innovation Promotion Association CAS[20200920] ; Beijing Natural Science Foundation[L192014] ; CAMS Innovation Fund for Medical Sciences (CIFMS)[2019-I2M-5-026]

Microbiology

Microbiology

WOS:000823133400001

AMER SOC MICROBIOLOGY

Web of Science

1.Capital Med Univ, Beijing Childrens Hosp,Res Unit Crit Infect Child, Chinese Acad Med Sci,Beijing Pediat Res Inst,Lab, Minist Educ,Natl Clin Res Ctr Resp Dis,Natl Ctr C, Beijing, Peoples R China
2.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China
3.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen, Peoples R China
4.Southern Univ Sci & Technol, Cryo EM Ctr, Dept Biol, Shenzhen, Peoples R China
5.Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Natl Lab Poliomyelitis,Natl Hlth Commiss Key Lab, WHO WPRO Reg Polio Reference Lab,Natl Hlth Commis, Beijing, Peoples R China
6.Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan, Peoples R China
7.Sun Yat Sen Univ, Zhongshan Sch Med, Inst Human Virol, Key Lab Trop Dis Control,Minist Educ, Guangzhou, Guangdong, Peoples R China
8.Univ Sci & Technol China, Div Life Sci & Med, Hefei, Peoples R China
9.Peking Univ, Genome Editing Res Ctr, Biomed Pioneering Innovat Ctr,State Key Lab Prot, Beijing Adv Innovat Ctr Genom,Peking Tsinghua Ctr, Beijing, Peoples R China
10.Chinese Acad Sci, CAS Ctr Influenza Res & Early Warning CASCIRE, Beijing, Peoples R China

Chen, Xiangpeng,Qu, Xiao,Liu, Congcong,et al. Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18[J]. mBio,2022.

Chen, Xiangpeng.,Qu, Xiao.,Liu, Congcong.,Zhang, Yong.,Zhang, Guigen.,...&Xie, Zhengde.(2022).Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18.mBio.

Chen, Xiangpeng,et al."Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18".mBio (2022).