Characterization of the GBoV1 Capsid and Its Antibody Interactions
Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in seve...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/2/330 |
| _version_ | 1797395769073860608 |
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| author | Jennifer Chun Yu Mario Mietzsch Amriti Singh Alberto Jimenez Ybargollin Shweta Kailasan Paul Chipman Nilakshee Bhattacharya Julia Fakhiri Dirk Grimm Amit Kapoor Indrė Kučinskaitė-Kodzė Aurelija Žvirblienė Maria Söderlund-Venermo Robert McKenna Mavis Agbandje-McKenna |
| author_facet | Jennifer Chun Yu Mario Mietzsch Amriti Singh Alberto Jimenez Ybargollin Shweta Kailasan Paul Chipman Nilakshee Bhattacharya Julia Fakhiri Dirk Grimm Amit Kapoor Indrė Kučinskaitė-Kodzė Aurelija Žvirblienė Maria Söderlund-Venermo Robert McKenna Mavis Agbandje-McKenna |
| author_sort | Jennifer Chun Yu |
| collection | DOAJ |
| description | Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties. |
| first_indexed | 2024-03-09T00:40:26Z |
| format | Article |
| id | doaj.art-44a5004850054f418bcd4dc8d9e1ce4e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T00:40:26Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-44a5004850054f418bcd4dc8d9e1ce4e2023-12-11T17:52:15ZengMDPI AGViruses1999-49152021-02-0113233010.3390/v13020330Characterization of the GBoV1 Capsid and Its Antibody InteractionsJennifer Chun Yu0Mario Mietzsch1Amriti Singh2Alberto Jimenez Ybargollin3Shweta Kailasan4Paul Chipman5Nilakshee Bhattacharya6Julia Fakhiri7Dirk Grimm8Amit Kapoor9Indrė Kučinskaitė-Kodzė10Aurelija Žvirblienė11Maria Söderlund-Venermo12Robert McKenna13Mavis Agbandje-McKenna14Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USABiological Science Imaging Resource, Department of Biological Sciences, Florida State University, Tallahassee, FL 32306, USADepartment of Infectious Diseases/Virology, Medical Faculty, BioQuant, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Infectious Diseases/Virology, Medical Faculty, BioQuant, University of Heidelberg, 69120 Heidelberg, GermanyCenter for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43220, USADepartment of Immunology and Cell Biology of the Institute of Biotechnology of Vilnius University, 10257 Vilnius, LithuaniaDepartment of Immunology and Cell Biology of the Institute of Biotechnology of Vilnius University, 10257 Vilnius, LithuaniaDepartment of Virology, University of Helsinki, 00014 Helsinki, FinlandDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USAHuman bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties.https://www.mdpi.com/1999-4915/13/2/330bocaviruscapsidparvoviruscryo-EMgene therapyantigenicity |
| spellingShingle | Jennifer Chun Yu Mario Mietzsch Amriti Singh Alberto Jimenez Ybargollin Shweta Kailasan Paul Chipman Nilakshee Bhattacharya Julia Fakhiri Dirk Grimm Amit Kapoor Indrė Kučinskaitė-Kodzė Aurelija Žvirblienė Maria Söderlund-Venermo Robert McKenna Mavis Agbandje-McKenna Characterization of the GBoV1 Capsid and Its Antibody Interactions Viruses bocavirus capsid parvovirus cryo-EM gene therapy antigenicity |
| title | Characterization of the GBoV1 Capsid and Its Antibody Interactions |
| title_full | Characterization of the GBoV1 Capsid and Its Antibody Interactions |
| title_fullStr | Characterization of the GBoV1 Capsid and Its Antibody Interactions |
| title_full_unstemmed | Characterization of the GBoV1 Capsid and Its Antibody Interactions |
| title_short | Characterization of the GBoV1 Capsid and Its Antibody Interactions |
| title_sort | characterization of the gbov1 capsid and its antibody interactions |
| topic | bocavirus capsid parvovirus cryo-EM gene therapy antigenicity |
| url | https://www.mdpi.com/1999-4915/13/2/330 |
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