Human adeno-associated virus type 5 is only distantly related to other known primate helper-dependent parvoviruses

Human adeno-associated virus type 5 is only distantly related to other known primate helper-dependent parvoviruses
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DOI:
10.1128/jvi.73.2.939-947.1999
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发表时间:
1999-02-01
影响因子:
5.4
通讯作者:
zur Hausen, H
zur Hausen, H
中科院分区:
医学2区
文献类型:
--
作者:
Bantel-Schaal, U;Delius, H;zur Hausen, H

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我们已经表征了5型腺相关病毒(AAV 5)基因组的95%(4,404个核苷酸),包括部分末端重复序列和末端解析位点。我们的结果显示,AAV 5在核苷酸水平和氨基酸水平上不同于所有其他描述的AAV血清型。与AAV 2、AAV 3B、AAV 4和AAV 6在核苷酸水平上的序列同源性仅在54%和56%之间。正链含有两个大的开放阅读框(ORF)。左边的ORF编码非结构蛋白(Rep),右边的ORF编码结构蛋白(Cap)。在氨基酸水平上,与其它AAV的衣壳蛋白的同一性在51%和59%之间的范围内,在被认为在病毒衣壳的外表面上的区域中具有高度的异质性。非结构Rep蛋白在氨基酸水平上的总体同一性为54.4%。在C-末端128个氨基酸处最低(10%)。在Rep蛋白中只有两个而不是常见的三个推定的锌指。Cap蛋白数据表明衣壳表面的差异,并提出了与其他细小病毒不同的宿主范围的可能性。这可能对用于基因治疗的AAV载体具有重要意义。
We have characterized 95% (4,404 nucleotides) of the genome of adeno-associated virus type 5 (AAV5), including part of the terminal repeats and the terminal resolution site. Our results show that AAV5 is different from all other described AAV serotypes at the nucleotide level and at the amino acid level. The sequence homology to AAV2, AAV3B, AAV4, and AAV6 at the nucleotide level is only between 54 and 56%. The positive strand contains two large open reading frames (ORFs). The left ORF encodes the nonstructural (Rep) proteins, and the right ORF encodes the structural (Cap) proteins. At the amino acid level the identities with the capsid proteins of other AAVs range between 51 and 59%, with a high degree of heterogeneity in regions which are considered to be on the exterior surface of the viral capsid. The overall identity for the nonstructural Rep proteins at the amino acid level is 54.4%. It is lowest at the C-terminal 128 amino acids (10%). There are only two instead of the common three putative Zn fingers in the Rep proteins. The Cap protein data suggest differences in capsid surfaces and raise the possibility of a host range distinct from those of other parvoviruses. This may have important implications for AAV vectors used in gene therapy.