AAV Capsid Structure and Cell Interactions
AAV Capsid Structure and Cell Interactions
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DOI：
10.1007/978-1-61779-370-7_3
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Kleinschmidt, Juergen
中科院分区：
文献类型：
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作者：
Agbandje-McKenna, Mavis;Kleinschmidt, Juergen
腺相关病毒（AAV）不与任何疾病相关，并且它们包装非基因组DNA和扩增不同细胞/组织群体的能力在理解它们的基础生物学以努力改善它们用于校正基因递送的利用方面产生了显著的兴趣。这包括它们的衣壳结构、细胞向性和用于进入、脱壳、复制、DNA包装、衣壳组装和抗体中和的相互作用。人和非人灵长类AAV被聚类为血清学上不同的遗传进化枝和血清型组，其具有不同的细胞/组织向性和转导效率。这些性质高度依赖于AAV衣壳氨基酸序列、其衣壳结构和其与宿主细胞flictors的相互作用，所述宿主细胞flictors包括细胞表面受体、共受体、信号传导分子、参与宿主DNA复制的蛋白质和宿主来源的抗体。本章回顾了目前的结构信息AAV衣壳和衣壳病毒蛋白区域发挥作用的细胞相互作用赋予感染性表型，然后用于注释衣壳的功能区域。基于目前的数据，表明AAV与细小病毒科的其他成员和形成T=1衣壳的其他ssDNA病毒一样，已经进化出具有保守核心区的多功能衣壳，这是有效衣壳运输、衣壳组装和基因组包装所需的。不同的表面环结构赋予不同的受体识别并参与抗体识别。结构区域在衣壳脱壳中的作用仍有待阐明。
The Adeno-associated viruses (AAVs) are not associated with any diseases, and their ability to package non-genomic DNA and to transduce different cell/tissue populations has generated significant interest in understanding their basic biology in efforts to improve their utilization for corrective gene delivery. This includes their capsid structure, cellular tropism and interactions for entry, uncoating, replication, DNA packaging, capsid assembly, and antibody neutralization. The human and nonhuman primate AAVs are clustered into serologically distinct genetic clade and serotype groups, which have distinct cellular/tissue tropisms and transduction efficiencies. These properties are highly dependent upon the AAV capsid amino acid sequence, their capsid structure, and their interactions with host cell flictors, including cell surface receptors, co-receptors, signaling molecules, proteins involved in host DNA replication, and host-derived antibodies. This chapter reviews the current structural information on AAV capsids and the capsid viral protein regions playing a role in the cellular interactions conferring an infective phenotype, which are then used to annotate the functional regions of the capsid. Based on the current data, the indication is that the AAVs, like other members of the Parvoviridae and other ssDNA viruses that form a T=1 capsid, have evolved a multifunctional capsid with conserved core regions as is required for efficient capsid trafficking, capsid assembly, and genome packaging. Disparate surface loop structures confer differential receptor recognition and are involved in antibody recognition. The role of structural regions in capsid uncoating remains to be elucidated.