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

Chen, Xiangpeng; Qu, Xiao; Liu, Congcong; Zhang, Yong; Zhang, Guigen; Han, Pu; Duan, Ying; Li, Qi; Wang, Liang; Ruan, Wenjing; Wang, Peiyi; Wei, Wensheng; Gao, Lidong; Zhao, Xin; Xie, Zhengde

doi:10.1128/mbio.01166-22

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…This finding is in alignment with our previous observation, that both ZIKV and its envelope glycoprotein E can enter and passage through MDCK/FcRn cells at higher levels than MDCK/vector cells [12]. It is possible that E protein interacts directly with FcRn, as has been reported for other viruses [21,22]; however, our binding studies to detect direct interaction of purified envelope glycoprotein and FcRn did not yield positive results (data not shown).…”

Section: Discussionsupporting

confidence: 92%

Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines

Momben-Abolfath

et al. 2022

Vaccines

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As a developmental toxicant, Zika virus (ZIKV) attacks both the growing nervous system, causing congenital Zika syndrome, and the placenta, resulting in pathological changes and associated adverse fetal outcomes. There are no vaccines, antibodies, or other treatments for ZIKV, despite the potential for its re-emergence. Multiple studies have highlighted the risk of antibodies for enhancing ZIKV infection, including during pregnancy, but the mechanisms for such effects are not fully understood. We have focused on the ability of the neonatal Fc receptor (FcRn) to interact with ZIKV in the presence and absence of relevant antibodies. We found that ZIKV replication was higher in Marvin Darby Canine Kidney (MDCK) cells that overexpress FcRn compared to those that do not, and knocking down FcRn decreased ZIKV RNA production. In the placenta trophoblast BeWo cell line, ZIKV infection itself downregulated FcRn at the mRNA and protein levels. Addition of anti-ZIKV antibodies to MDCK/FcRn cells resulted in non-monotonous neutralization curves with neutralization attenuation and even enhancement of infection at higher concentrations. Non-monotonous neutralization was also seen in BeWo cells at intermediate antibody concentrations. Our studies highlight the underappreciated role FcRn plays in ZIKV infection and may have implications for anti-ZIKV prophylaxis and therapy in pregnant women.

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Section: Discussionsupporting

confidence: 92%

Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines

Momben-Abolfath

et al. 2022

Vaccines

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“…Human FcRn has been demonstrated to be a two-in-one attachment-uncoating receptor of E18, and we hypothesize that this receptor plays a similar role in E30 invasion, because siRNA knockdown of DAF alone does not prevent E30 invasion, but siRNA treatment of FcRn completely abolishes E30 infection, as previously mentioned (Vandesande et al, 2020;Chen et al, 2022). Although FcRn plays an important role in E30 viral decapitation and is a necessary receptor for E30 invasion, studies have demonstrated that human FcRn expression is insufficient to infect echovirus through an in vivo pathway of the gastrointestinal tract; Type I IFN is a major driver of echovirus transmission from the gastrointestinal tract to secondary sites, including the liver and pancreas; and Type III IFN inhibits persistent echovirus infection in gastrointestinal epithelial cells (Wells et al, 2021(Wells et al, , 2022.…”

Section: Downstream Pathwayssupporting

confidence: 54%

Investigating the mechanism of Echovirus 30 cell invasion

et al. 2023

Self Cite

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Viruses invade susceptible cells through a complex mechanism before injecting their genetic material into them. This causes direct damage to the host cell, as well as resulting in disease in the corresponding system. Echovirus type 30 (E30) is a member of the Enterovirus B group and has recently been reported to cause central nervous system (CNS) disorders, leading to viral encephalitis and viral meningitis in children. In this review, we aim to help in improving the understanding of the mechanisms of CNS diseases caused by E30 for the subsequent development of relevant drugs and vaccines.

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“…Indeed, our screening results paralleled a recent report identifying critical host factors for echovirus 6, in which FCGRT, CD55, and B2M emerged as the top three hits 17 . While CD55 serves as a critical receptor for echovirus attachment 29 , FcRn is involved in echovirus uncoating and genome release 17,30 . HAstV may share similar entry mechanisms, with DPP4 replacing the activity of CD55.…”

Section: Pharmacological Inhibition Of Fcrn or Dpp4 Prevents Hastv In...mentioning

confidence: 99%

The neonatal Fc receptor and DPP4 are human astrovirus receptors

Ingle,

Molleston,

Hall

et al. 2024

Preprint

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Human astroviruses (HAstV) are major global causes of gastroenteritis, but little is known about host factors required for their cellular entry. Here, we utilized complementary CRISPR-Cas9-based knockout and activation screening approaches and identified neonatal Fc receptor (FcRn) and dipeptidyl-peptidase IV (DPP4) as entry factors for HAstV infection of human intestinal epithelial cells. Disruption of FcRn or DPP4 reduced HAstV infection in permissive cells and, reciprocally, overexpression of these factors in non-permissive cells was sufficient to promote infection. We observed direct binding between FcRn and HAstV virions as well as purified spike protein. Finally, inhibitors for DPP4 and FcRn currently in clinical use prevent HAstV infection in cell lines and primary human enteroids. Thus, our results reveal mechanisms of HAstV entry as well as druggable targets.One-Sentence SummaryTargeting FcRn or DPP4 using available therapies effectively prevents human astrovirus infection in human enteroid cultures.

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

Abstract: 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.

Cited by 10 publications

References 40 publications

Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines

Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines

Investigating the mechanism of Echovirus 30 cell invasion

The neonatal Fc receptor and DPP4 are human astrovirus receptors

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