Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA.
J Virol. 2013 May;87(9):5128-40. doi: 10.1128/JVI.03416-12. Epub 2013 Feb 28.
The structure of single-stranded DNA (ssDNA) packaging H-1 parvovirus (H-1PV), which is being developed as an antitumor gene delivery vector, has been determined for wild-type (wt) virions and noninfectious (empty) capsids to 2.7- and 3.2-Å resolution, respectively, using X-ray crystallography. The capsid viral protein (VP) structure consists of an α-helix and an eight-stranded anti-parallel β-barrel with large loop regions between the strands. The β-barrel and loops form the capsid core and surface, respectively. In the wt structure, 600 nucleotides are ordered in an interior DNA binding pocket of the capsid. This accounts for ∼12% of the H-1PV genome. The wt structure is identical to the empty capsid structure, except for side chain conformation variations at the nucleotide binding pocket. Comparison of the H-1PV nucleotides to those observed in canine parvovirus and minute virus of mice, two members of the genus Parvovirus, showed both similarity in structure and analogous interactions. This observation suggests a functional role, such as in capsid stability and/or ssDNA genome recognition for encapsulation. The VP structure differs from those of other parvoviruses in surface loop regions that control receptor binding, tissue tropism, pathogenicity, and antibody recognition, including VP sequences reported to determine tumor cell tropism for oncotropic rodent parvoviruses. These structures of H-1PV provide insight into structural features that dictate capsid stabilization following genome packaging and three-dimensional information applicable for rational design of tumor-targeted recombinant gene delivery vectors.
H-1 细小病毒（H-1PV）是一种正在被开发为抗肿瘤基因传递载体的单链 DNA（ssDNA）包装 H-1 细小病毒，其野生型（wt）病毒体和非感染性（空）衣壳的结构已分别使用 X 射线晶体学确定至 2.7-和 3.2-Å分辨率。衣壳病毒蛋白（VP）结构由α-螺旋和八链反平行β-桶组成，链之间有大的环区。β-桶和环分别形成衣壳的核心和表面。在 wt 结构中，600 个核苷酸有序排列在衣壳的内部 DNA 结合口袋中。这占 H-1PV 基因组的约 12%。wt 结构与空衣壳结构相同，除了核苷酸结合口袋处侧链构象的变化。将 H-1PV 核苷酸与犬细小病毒和小鼠微小病毒（细小病毒属的两个成员）中观察到的核苷酸进行比较，发现结构相似且相互作用类似。这种观察表明存在功能作用，例如在衣壳稳定性和/或 ssDNA 基因组识别以进行包装。VP 结构与其他细小病毒的结构不同，在于控制受体结合、组织趋向性、致病性和抗体识别的表面环区，包括据报道决定致癌性啮齿动物细小病毒对肿瘤细胞趋向性的 VP 序列。这些 H-1PV 结构提供了有关结构特征的见解，这些特征决定了基因组包装后衣壳的稳定，以及适用于肿瘤靶向重组基因传递载体合理设计的三维信息。
