Characterization of the GBoV1 Capsid and Its Antibody Interactions.
Characterization of the GBoV1 Capsid and Its Antibody Interactions.
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DOI：
10.3390/v13020330
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发表时间：
2021-02-20
期刊：
影响因子：
--
通讯作者：
Agbandje-McKenna M
中科院分区：
文献类型：
--
作者：
Yu JC;Mietzsch M;Singh A;Jimenez Ybargollin A;Kailasan S;Chipman P;Bhattacharya N;Fakhiri J;Grimm D;Kapoor A;Kučinskaitė-Kodzė I;Žvirblienė A;Söderlund-Venermo M;McKenna R;Agbandje-McKenna M
人博卡病毒1型（humanbocavirus 1，HBoV 1）作为一种基因递送载体以其感染极化的人气道上皮细胞的能力和5.5kb的基因组包装容量而受到关注。大猩猩博卡病毒1（GBoV 1）VP 3与HBoV 1共享86%的氨基酸序列同一性，但在几种人类细胞类型中具有更好的转导效率。在这里，我们报告了GBoV 1的衣壳结构，使用冷冻电子显微镜（cryo-EM）确定为2.76 μ m的分辨率及其与小鼠单克隆抗体（mAb）和人血清的相互作用。GBoVl与其他细小病毒共享衣壳表面形态，在5倍对称轴处具有通道，围绕3倍轴的突起和2倍轴处的凹陷。一个2/5倍的壁将2倍轴和5倍轴分开。与皿oVl相比，差异局限于3重突起。一致地，天然斑点免疫印迹和冷冻-EM分别显示通过5倍靶向HBoVl mAb 15 C6的交叉反应性和结合。令人惊讶的是，观察到三种3倍靶向mAb中的一种12 C1的识别，表明在该区域存在一些结构相似性。此外，针对40份人血清测试的GBoVl显示出与HBoVl相似的血清阳性率。针对细小病毒载体的免疫原性反应是有效基因递送的重要障碍。这项研究是朝着优化具有抗体逃逸特性的博卡病毒载体迈出的一步。
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.
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DOI：
10.1086/652416
发表时间：
2010-06-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Kapoor A;Simmonds P;Slikas E;Li L;Bodhidatta L;Sethabutr O;Triki H;Bahri O;Oderinde BS;Baba MM;Bukbuk DN;Besser J;Bartkus J;Delwart E
通讯作者：
Delwart E
影响因子：
6.4
作者：
BATES, RC;STORZ, J;REED, DE
通讯作者：
REED, DE
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
Kailasan, Shweta;Garrison, Jamie;Agbandje-McKenna, Mavis
通讯作者：
Agbandje-McKenna, Mavis
DOI：
10.1073/pnas.0504666102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Allander, T;Tammi, MT;Andersson, B
通讯作者：
Andersson, B