Abstract
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.
Highlights
Gorilla bocavirus 1 (GBoV1) is a member of the genus Bocaparvovirus in the Parvoviridae that contain single-stranded DNA packaging viruses [1]
We report the high-resolution structure of the GBoV1 capsid, determined by cryo-electron microscopy and 3D single-particle reconstruction
The Bac-to-Bac baculovirus system was used for the expression of human bocavirus 1 (HBoV1), HBoV4, GBoV1, associated virus serotype 2 (AAV2) and AAV5 virus-like particles (VLPs) as described previously for HBoV1 (VP3 only), AAV2 and AAV5 [22,34]
Summary
Gorilla bocavirus 1 (GBoV1) is a member of the genus Bocaparvovirus in the Parvoviridae that contain single-stranded DNA (ssDNA) packaging viruses [1]. The family is divided into three subfamilies, including the subfamily Parvovirinae whose members infect vertebrate hosts [1]. Bocaparvoviruses represents the largest genus in this subfamily, with 21 classified species that infect a variety of hosts, including cows, rabbits, rodents, humans and non-human primates [2,3,4,5,6,7,8,9,10]. The first discovered member infecting humans is human bocavirus 1 (HBoV1), isolated in 2005 from nasopharyngeal aspirates of children under 2 years of age with acute respiratory infections [7]. GBoV1 was isolated from gorillas with enteritis and is the first identified non-human primate bocavirus [10]
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