期刊
VIRUSES-BASEL
卷 13, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/v13020330
关键词
bocavirus; capsid; parvovirus; cryo-EM; gene therapy; antigenicity
类别
资金
- National Health Institute [NIH R01 GM02946]
- Sigrid Juselius Foundation
- Cystic Fibrosis Foundation (CFF) grant [GRIMM15XX0]
- Life and Health Medical Foundation
The study reports the capsid structure of Gorilla bocavirus 1 (GBoV1) and its interactions with human sera and monoclonal antibodies. GBoV1 shares similarities with Human bocavirus 1 (HBoV1) but shows differences in specific structural regions. Furthermore, GBoV1 demonstrates comparable seropositivity rates to HBoV1 when tested against human sera.
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 angstrom 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.
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