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

Xu, Yanqun; He, Yong; Momben-Abolfath, Sanaz; Vertrees, Devin; Li, Xiaohong; Norton, Malgorzata G.; Struble, Evi Budo

doi:10.3390/vaccines10122059

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

Journal Article · Wed Nov 30 04:00:00 EST 2022 · Vaccines

DOI:https://doi.org/10.3390/vaccines10122059· OSTI ID:2471223

Xu, Yanqun ^[1]; He, Yong ^[1]; Momben-Abolfath, Sanaz ^[1]; Vertrees, Devin ^[1]; Li, Xiaohong ^[1]; Norton, Malgorzata G. ^[1]; ^[1]

US Food and Drug Administration (USFDA), Silver Spring, MD (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471223

Journal Information:: Vaccines, Journal Name: Vaccines Journal Issue: 12 Vol. 10; ISSN 2076-393X

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (28)

Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians Moore, Cynthia A.; Staples, J. Erin; Dobyns, William B. JAMA Pediatrics, Vol. 171, Issue 3 https://doi.org/10.1001/jamapediatrics.2016.3982	journal	March 2017
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure Qian, Xuyu; Nguyen, Ha Nam; Song, Mingxi M. Cell, Vol. 165, Issue 5 https://doi.org/10.1016/j.cell.2016.04.032	journal	May 2016
Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B Zhao, Xin; Zhang, Guigen; Liu, Sheng Cell, Vol. 177, Issue 6 https://doi.org/10.1016/j.cell.2019.04.035	journal	May 2019
Fc Glycan-Mediated Regulation of Placental Antibody Transfer Jennewein, Madeleine F.; Goldfarb, Ilona; Dolatshahi, Sepideh Cell, Vol. 178, Issue 1 https://doi.org/10.1016/j.cell.2019.05.044	journal	June 2019
In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies Li, Dapeng; Edwards, Robert J.; Manne, Kartik Cell, Vol. 184, Issue 16 https://doi.org/10.1016/j.cell.2021.06.021	journal	August 2021
Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages Zimmerman, Matthew G.; Quicke, Kendra M.; O'Neal, Justin T. Cell Host & Microbe, Vol. 24, Issue 5 https://doi.org/10.1016/j.chom.2018.10.008	journal	November 2018
Human Neonatal Fc Receptor Mediates Transport of IgG into Luminal Secretions for Delivery of Antigens to Mucosal Dendritic Cells Yoshida, Masaru; Claypool, Steven M.; Wagner, Jessica S. Immunity, Vol. 20, Issue 6 https://doi.org/10.1016/j.immuni.2004.05.007	journal	June 2004
Expression of the neonatal Fc-receptor in placental-fetal endothelium and in cells of the placental immune system Kiskova, Terezia; Mytsko, Yuliya; Schepelmann, Martin Placenta, Vol. 78 https://doi.org/10.1016/j.placenta.2019.02.012	journal	March 2019
Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates Wang, Qidi; Zhang, Lianfeng; Kuwahara, Kazuhiko ACS Infectious Diseases, Vol. 2, Issue 5 https://doi.org/10.1021/acsinfecdis.6b00006	journal	March 2016
Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology Hirsch, Alec J.; Roberts, Victoria H. J.; Grigsby, Peta L. Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-017-02499-9	journal	January 2018
A human endothelial cell-based recycling assay for screening of FcRn targeted molecules Grevys, Algirdas; Nilsen, Jeannette; Sand, Kine M. K. Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-03061-x	journal	February 2018
Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor Liu, Xiaoyang; Palaniyandi, Senthilkumar; Zhu, Iowis Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-10865-y	journal	July 2019
ZIKV can infect human term placentas in the absence of maternal factors Villazana-Kretzer, Diana L.; Wuertz, Kathryn McGuckin; Newhouse, Daniel Communications Biology, Vol. 5, Issue 1 https://doi.org/10.1038/s42003-022-03158-6	journal	March 2022
The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier mAbs, Vol. 7, Issue 2 https://doi.org/10.1080/19420862.2015.1008353	journal	January 2015
An in vitro FcRn- dependent transcytosis assay as a screening tool for predictive assessment of nonspecific clearance of antibody therapeutics in humans Chung, Shan; Nguyen, Van; Lin, Yuwen Linda mAbs, Vol. 11, Issue 5 https://doi.org/10.1080/19420862.2019.1605270	journal	April 2019
Zika Virus Changes Methylation of Genes Involved in Immune Response and Neural Development in Brazilian Babies Born With Congenital Microcephaly Anderson, Denise; Neri, João I. C. F.; Souza, Cássio R. M. The Journal of Infectious Diseases, Vol. 223, Issue 3 https://doi.org/10.1093/infdis/jiaa383	journal	July 2020
Maternal Zika Virus Infection Cooper, Hannah J.; Iwamoto, Martha; Lash, Maura Obstetrics & Gynecology, Vol. 134, Issue 6 https://doi.org/10.1097/AOG.0000000000003577	journal	November 2019
Zika infection and the development of neurological defects Russo, Fabiele Baldino; Jungmann, Patricia; Beltrão-Braga, Patricia Cristina Baleeiro Cellular Microbiology, Vol. 19, Issue 6 https://doi.org/10.1111/cmi.12744	journal	May 2017
The multiple facets of FcRn in immunity Stapleton, Nigel M.; Einarsdóttir, Helga K.; Stemerding, Annette M. Immunological Reviews, Vol. 268, Issue 1 https://doi.org/10.1111/imr.12331	journal	October 2015
Maternal immunity and antibodies to dengue virus promote infection and Zika virus–induced microcephaly in fetuses Rathore, Abhay P. S.; Saron, Wilfried A. A.; Lim, Ting Science Advances, Vol. 5, Issue 2 https://doi.org/10.1126/sciadv.aav3208	journal	February 2019
Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection Stettler, K.; Beltramello, M.; Espinosa, D. A. Science, Vol. 353, Issue 6301 https://doi.org/10.1126/science.aaf8505	journal	July 2016
Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry Wan, Yushun; Shang, Jian; Sun, Shihui Journal of Virology, Vol. 94, Issue 5 https://doi.org/10.1128/JVI.02015-19	journal	December 2019
Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18 Chen, Xiangpeng; Qu, Xiao; Liu, Congcong mBio, Vol. 13, Issue 4 https://doi.org/10.1128/mbio.01166-22	journal	August 2022
Adverse fetal and neonatal outcomes in pregnancies with confirmed Zika Virus infection in Rio de Janeiro, Brazil: A cohort study Souza, Juliana P.; Méio, Maria Dalva B. B.; de Andrade, Laura Medeiros PLOS Neglected Tropical Diseases, Vol. 15, Issue 1 https://doi.org/10.1371/journal.pntd.0008893	journal	January 2021
The Neonatal Fc Receptor (FcRn): A Misnomer? Pyzik, Michal; Sand, Kine M. K.; Hubbard, Jonathan J. Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01540	journal	July 2019
Zika Induces Human Placental Damage and Inflammation Rabelo, Kíssila; de Souza, Luiz José; Salomão, Natália Gedeão Frontiers in Immunology, Vol. 11 https://doi.org/10.3389/fimmu.2020.02146	journal	September 2020
ZIKV Infection and miRNA Network in Pathogenesis and Immune Response Polonio, Carolina Manganeli; Peron, Jean Pierre Schatzmann Viruses, Vol. 13, Issue 10 https://doi.org/10.3390/v13101992	journal	October 2021
Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface Xu, Yanqun; He, Yong; Momben-Abolfath, Sanaz Vaccines, Vol. 9, Issue 2 https://doi.org/10.3390/vaccines9020145	journal	February 2021

Similar Records

Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface

Journal Article · Sun Jan 31 23:00:00 EST 2021 · Vaccines · OSTI ID:1817039

NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice

Journal Article · Tue Dec 10 23:00:00 EST 2019 · Science Advances · OSTI ID:1591849

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Journal Article · Wed Aug 09 00:00:00 EDT 2023 · Cell Reports · OSTI ID:2470065

Related Subjects

60 APPLIED LIFE SCIENCES
FcRn
anti-viral antibody responses
antibody-dependent enhancement (ADE)
flavivirus
immunology
research & experimental medicine
virus–host interactions
zika virus

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

Citation Formats

References (28)

Similar Records

Related Subjects