Characterization of the GBoV1 Capsid and Its Antibody Interactions
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
Affiliations
Jennifer Chun Yu
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Mario Mietzsch
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Amriti Singh
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Alberto Jimenez Ybargollin
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Shweta Kailasan
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Paul Chipman
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Nilakshee Bhattacharya
Biological Science Imaging Resource, Department of Biological Sciences, Florida State University, Tallahassee, FL 32306, USA
Julia Fakhiri
Department of Infectious Diseases/Virology, Medical Faculty, BioQuant, University of Heidelberg, 69120 Heidelberg, Germany
Dirk Grimm
Department of Infectious Diseases/Virology, Medical Faculty, BioQuant, University of Heidelberg, 69120 Heidelberg, Germany
Amit Kapoor
Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43220, USA
Indrė Kučinskaitė-Kodzė
Department of Immunology and Cell Biology of the Institute of Biotechnology of Vilnius University, 10257 Vilnius, Lithuania
Aurelija Žvirblienė
Department of Immunology and Cell Biology of the Institute of Biotechnology of Vilnius University, 10257 Vilnius, Lithuania
Maria Söderlund-Venermo
Department of Virology, University of Helsinki, 00014 Helsinki, Finland
Robert McKenna
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Mavis Agbandje-McKenna
Department of Biochemistry and Molecular Biology, Center for Structural Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
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.
