Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/12/2059 |
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| author | Yanqun Xu Yong He Sanaz Momben-Abolfath Devin Vertrees Xiaohong Li Malgorzata G. Norton Evi Budo Struble |
| author_facet | Yanqun Xu Yong He Sanaz Momben-Abolfath Devin Vertrees Xiaohong Li Malgorzata G. Norton Evi Budo Struble |
| author_sort | Yanqun Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:45:30Z |
| format | Article |
| id | doaj.art-255d728aeadc462aa6a5085eebcf2527 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T15:45:30Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-255d728aeadc462aa6a5085eebcf25272023-11-24T18:31:59ZengMDPI AGVaccines2076-393X2022-11-011012205910.3390/vaccines10122059Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell LinesYanqun Xu0Yong He1Sanaz Momben-Abolfath2Devin Vertrees3Xiaohong Li4Malgorzata G. Norton5Evi Budo Struble6Laboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USALaboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USALaboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USALaboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USALaboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USALaboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USALaboratory of Plasma Derivatives, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USAAs 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.https://www.mdpi.com/2076-393X/10/12/2059Zika virusflavivirusanti-viral antibody responsesvirus–host interactionsantibody-dependent enhancement (ADE)FcRn |
| spellingShingle | Yanqun Xu Yong He Sanaz Momben-Abolfath Devin Vertrees Xiaohong Li Malgorzata G. Norton Evi Budo Struble Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines Vaccines Zika virus flavivirus anti-viral antibody responses virus–host interactions antibody-dependent enhancement (ADE) FcRn |
| title | Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines |
| title_full | Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines |
| title_fullStr | Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines |
| title_full_unstemmed | Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines |
| title_short | Zika Virus Infection and Antibody Neutralization in FcRn Expressing Placenta and Engineered Cell Lines |
| title_sort | zika virus infection and antibody neutralization in fcrn expressing placenta and engineered cell lines |
| topic | Zika virus flavivirus anti-viral antibody responses virus–host interactions antibody-dependent enhancement (ADE) FcRn |
| url | https://www.mdpi.com/2076-393X/10/12/2059 |
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