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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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Main Authors: Yu, Jennifer Chun (Author) , Mietzsch, Mario (Author) , Singh, Amriti (Author) , Jimenez Ybargollin, Alberto (Author) , Kailasan, Shweta (Author) , Chipman, Paul (Author) , Bhattacharya, Nilakshee (Author) , Fakhiri, Julia (Author) , Grimm, Dirk (Author) , Kapoor, Amit (Author) , Kučinskaitė-Kodzė, Indrė (Author) , Žvirblienė, Aurelija (Author) , Söderlund-Venermo, Maria (Author) , McKenna, Robert (Author) , Agbandje-McKenna, Mavis (Author)
Format: Article (Journal)
Language:English
Published: 10 February 2021
In: Viruses
Year: 2021, Volume: 13, Issue: 2, Pages: 1-17
ISSN:1999-4915
DOI:10.3390/v13020330
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/v13020330
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4915/13/2/330
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Author Notes: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 and Mavis Agbandje-McKenna
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Summary: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.
Item Description:Gesehen am 26.08.2021
Physical Description:Online Resource
ISSN:1999-4915
DOI:10.3390/v13020330

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