Structural characterization of a bat Adeno-associated virus capsid.
Structural characterization of a bat Adeno-associated virus capsid.
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DOI：
10.1016/j.jsb.2020.107547
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发表时间：
2020-08-01
影响因子：
3
通讯作者：
Agbandje-McKenna, Mavis
中科院分区：
文献类型：
--
作者：
Mietzsch, Mario;Li, Ya;Kurian, Justin;Smith, James Kennon;Chipman, Paul;McKenna, Robert;Yang, Lin;Agbandje-McKenna, Mavis
腺相关病毒(AAVs)广泛存在于脊椎动物中。从蝙蝠中分离的AAVs具有与AAV2、AAV5和其他灵长类AAVs的低衣壳蛋白序列同源性(<；60%)。在这里，我们报道了从蝙蝠中分离到的第一个非灵长类AAV的衣壳结构。BtAAV-10HB(10HB)的衣壳结构是用低温电子显微镜和三维图像重建技术确定的。对空颗粒和含基因组颗粒的比较表明，衣壳结构几乎相同，除了前面描述的核苷酸结合口袋中的有序核苷酸，5倍通道中的密度，以及几个侧链构象改变的氨基酸。与其他依赖病毒如AAV2和AAV5相比，10HB具有独特的结构特征，包括衣壳表面环的插入和缺失。总体而言，10HB衣壳结构与AAV2和AAV5的RMSD分别为1.7？和1.8？目前，所有临床试验中批准的AAV人类基因治疗生物制品和载体都是基于灵长类分离株。然而，人类人口中预先存在的中和抗体是使用它们的障碍。10HB衣壳具有包装AAV2载体基因组的能力，因此具有作为基因输送载体的潜力。值得注意的是，在含有人血清的屏幕上，10HB衣壳缺乏识别。因此，10HB载体不同的衣壳表面很可能使其对潜在的预先存在的中和人类抗体“看不见”，特别是因为这种病毒或类似的变种在灵长类种群中不存在。
Adeno-associated viruses (AAVs) are widespread among vertebrates. AAVs isolated from bats display low capsid protein sequence identities (<60%) to AAV2, AAV5, and other primate AAVs. Here we report the first capsid structure of a non-primate AAV which was isolated from bats. The capsid structure of BtAAV-10HB (10HB) was determined by cryo-electron microscopy and three-dimensional image reconstruction to 3.0 Å resolution. Comparison of empty and genome-containing particles showed that the capsid structures are almost identical except for an ordered nucleotide in a previously described nucleotide-binding pocket, the density in the 5-fold channel, and several amino acids with altered side chain conformations. Compared to other dependoparvoviruses, for example AAV2 and AAV5, 10HB displays unique structural features including insertions and deletions in capsid surface loops. Overall, the 10HB capsid structure superposes with an RMSD of 1.7 Å and 1.8 Å to AAV2 and AAV5, respectively. Currently all approved AAV human gene therapy biologics and vectors in clinical trials are based on primate isolates. However, pre-existing neutralizing antibodies in the human population represents a hurdle to their use. 10HB capsids are capable of packaging AAV2 vector genomes and thus have potential as gene delivery vectors. Significantly, a screen with human sera showed lack of recognition by the 10HB capsid. Thus, the different capsid surface of 10HB vectors likely renders it “invisible” to potential pre-existing neutralizing human antibodies especially because this virus or similar variants do not exist in primate populations.
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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：
3.7
作者：
BANTELSCHAAL, U;HAUSEN, HZ
通讯作者：
HAUSEN, HZ
影响因子：
5.4
作者：
Govindasamy, Lakshmanan;DiMattia, Michael A.;Agbandje-McKenna, Mavis
通讯作者：
Agbandje-McKenna, Mavis
DOI：
10.3390/v10010022
发表时间：
2018-01-04
期刊：
Viruses
影响因子：
--
作者：
Ilyas M;Mietzsch M;Kailasan S;Väisänen E;Luo M;Chipman P;Smith JK;Kurian J;Sousa D;McKenna R;Söderlund-Venermo M;Agbandje-McKenna M
通讯作者：
Agbandje-McKenna M
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH