Phylogeny and primary structure analysis of fiber shafts of all human adenovirus types for rational design of adenoviral gene-therapy vectors
Phylogeny and primary structure analysis of fiber shafts of all human adenovirus types for rational design of adenoviral gene-therapy vectors
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DOI：
10.1099/vir.0.014514-0
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发表时间：
2009-12-01
影响因子：
3.8
通讯作者：
Heim, Albert
中科院分区：
文献类型：
--
作者：
Darr, Sebastian;Madisch, Ijad;Heim, Albert
人腺病毒（HAdV）的纤维轴对于使五邻体基底接近二级细胞受体是必不可少的。研究了所有53种HAdV类型的纤维轴序列。纤维轴的系统发育揭示了对应于HAdV物种概念的聚类。一个种内重组热点被发现在轴/旋钮边界，一个高度保守的序列延伸。例如，HAdV-D20在纤维轴中与HAdV-D23成簇，但在纤维节中与HAdV-D47成簇。虽然所有的轴表现出典型的假重复序列，氨基酸序列的同一性被认为是高达92%（种间）和54%（种内）。与先前的研究相反，在8种HAdV-D中发现了柔性基序（KXGGLXFD/N），而推定的硫酸乙酰肝素结合位点（KKTK）仅在HAdV-C中发现。我们的研究结果表明，在轴/旋钮边界的基因治疗载体的假型是可行的，但轴的灵活性数据应予以考虑。
The fiber shaft of human adenoviruses (HAdVs) is essential for bringing the penton base into proximity to the secondary cellular receptor. Fiber shaft sequences of all 53 HAdV types were studied. Phylogeny of the fiber shaft revealed clustering corresponding to the HAdV species concept. An intraspecies recombination hot spot was found at the shaft/knob boundary, a highly conserved sequence stretch. For example, HAdV-D20 clustered with HAdV-D23 in the fiber shaft, but with HAdV-D47 in the fiber knob. Although all shafts exhibited the typical pseudorepeats, amino acid sequence identity was found to be as high as 92% (interspecies) and 54% (intraspecies). in contrast to a previous study, a flexibility motif (KXGGLXFD/N) was found in eight HAdV-D types, whereas the putative heparan sulfate-binding site (KKTK) was only found in species HAdV-C. Our results suggest that pseudotyping of gene-therapy vectors at the shaft/knob boundary is feasible, but that flexibility data of shafts should be considered.