Three-dimensional structure of canine adenovirus serotype 2 capsid
Three-dimensional structure of canine adenovirus serotype 2 capsid
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DOI：
10.1128/jvi.02393-07
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
Kremer, Eric J.
中科院分区：
文献类型：
--
作者：
Schoelm, Guy;El Bakkouri, Majida;Kremer, Eric J.
已知的腺病毒（AdV）血清型超过100种，包括50种人血清型。由于腺病毒诱导的疾病是相对物种特异性的，来源于非人血清型的载体可能具有更广泛的临床潜力，部分原因是缺乏普遍存在的记忆免疫。尽管已经在结构水平上研究了一些人血清型衣壳，但没有分析非人血清型。人腺病毒（hAdV）的分析奠定的基础，使我们能够确定和比较犬血清型2（CAV-2）的衣壳的三维结构的hAdV血清型5（hAdV-5）。我们表明，CAV-2衣壳具有比人血清型更光滑的结构。在hAdV-5五邻体碱基和六邻体中发现的许多外部环（抗体反应针对其）在CAV-2中较短或不存在。另一方面，CAV-2光纤看起来更复杂，在轴中有两个弯曲。人和犬病毒之间的一个有趣的区别是，蛋白IX的C末端部分位于不同的位置，使CAV-2衣壳伸出天线。两种病毒之间的比较允许鉴定CAV-2衣壳上应该容易修饰的位点，以改变组织嗜性或其他生物活性。
There are more than 100 known adenovirus (AdV) serotypes, including 50 human serotypes. Because AdV-induced disease is relatively species specific, vectors derived from nonhuman serotypes may have wider clinical potential based, in part, on the lack of ubiquitous memory immunity. Whereas a few of the human serotype capsids have been studied at the structural level, none of the nonhuman serotypes has been analyzed. The basis laid by the analysis of human AdV (hAdV) has allowed us to determine and compare the three-dimensional structure of the capsid of canine serotype 2 (CAV-2) to that of hAdV serotype 5 (hAdV-5). We show that CAV-2 capsid has a smoother structure than the human serotypes. Many of the external loops found in the hAdV-5 penton base and the hexon, against which the antibody response is directed, are shorter or absent in CAV-2. On the other hand, the CAV-2 fiber appears to be more complex, with two bends in the shaft. An interesting difference between the human and canine viruses is that the C-terminal part of protein IX is in a different position, making an antenna sticking out of the CAV-2 capsid. The comparison between the two viruses allows the identification of sites that should be easy to modify on the CAV-2 capsid for altering tissue tropism or other biological activities.