Structure of adeno-associated virus type 4
Structure of adeno-associated virus type 4
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DOI：
10.1128/jvi.79.8.5047-5058.2005
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发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Agbandje-McKenna, M
中科院分区：
文献类型：
--
作者：
Padron, E;Bowman, V;Agbandje-McKenna, M
腺相关病毒（AAV）是细小病毒科的成员，属于依赖病毒属。目前，几种不同的 AAV 分离株正在开发用于人类基因治疗应用，因为它们能够转导不同的靶细胞。操纵 AAV 衣壳进行特定组织递送的需要引起了人们对了解其衣壳结构的兴趣。 4 型 AAV (AAV4) 是抗原性最独特的血清型之一，通过冷冻电子显微镜和图像重建以 13 埃的分辨率确定了其结构。通过使用其主要衣壳蛋白 VP3 与 AAV2 的基于结构的序列比对，为 AAV4 衣壳建立了伪原子模型，AAV4 与 AAV2 具有 58% 的相同性，并受到其重建的密度包膜的限制。该模型显示了表面环的变化，这可能解释了 AAV2 和 AAV4 之间受体结合和抗原性的差异。 AAV4衣壳表面拓扑结构还显示出与阿留申水貂病病毒和人细小病毒B19（该属的自主成员）的出乎意料的结构相似性，尽管序列同源性有限。
Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy applications due to their ability to transduce different target cells. The need to manipulate AAV capsids for specific tissue delivery has generated interest in understanding their capsid structures. The structure of AAV type 4 (AAV4), one of the most antigenically distinct serotypes, was determined to 13-angstrom resolution by cryo-electron microscopy and image reconstruction. A pseudoatomic model was built for the AAV4 capsid by use of a structure-based sequence alignment of its major capsid protein, VP3, with that of AAV2, to which AAV4 is 58% identical and constrained by its reconstructed density envelope. The model showed variations in the surface loops that may account for the, differences in receptor binding and antigenicity between AAV2 and AAV4. The AAV4 capsid surface topology also shows an unpredicted structural similarity to that of Aleutian mink disease virus and human parvovirus B19, autonomous members of the genus, despite limited sequence homology.