Fry Elizabeth E, Knowles Nick J, Newman John W I, Wilsden Ginette, Rao Zihe, King Andrew M Q, Stuart David I
Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, United Kingdom.
J Virol. 2003 May;77(9):5475-86. doi: 10.1128/jvi.77.9.5475-5486.2003.
Swine vesicular disease virus (SVDV) is an Enterovirus of the family Picornaviridae that causes symptoms indistinguishable from those of foot-and-mouth disease virus. Phylogenetic studies suggest that it is a recently evolved genetic sublineage of the important human pathogen coxsackievirus B5 (CBV5), and in agreement with this, it has been shown to utilize the coxsackie and adenovirus receptor (CAR) for cell entry. The 3.0-A crystal structure of strain UK/27/72 SVDV (highly virulent) reveals the expected similarity in core structure to those of other picornaviruses, showing most similarity to the closest available structure to CBV5, that of coxsackievirus B3 (CBV3). Features that help to cement together and rigidify the protein subunits are extended in this virus, perhaps explaining its extreme tolerance of environmental factors. Using the large number of capsid sequences available for both SVDV and CBV5, we have mapped the amino acid substitutions that may have occurred during the supposed adaptation of SVDV to a new host onto the structure of SVDV and a model of the SVDV/CAR complex generated by reference to the cryo-electron microscopy-visualized complex of CBV3 and CAR. The changes fall into three clusters as follows: one lines the fivefold pore, a second maps to the CAR-binding site and partially overlaps the site for decay accelerating factor (DAF) to bind to echovirus 7 (ECHO7), and the third lies close to the fivefold axis, where the low-density lipoprotein receptor binds to the minor group of rhinoviruses. Later changes in SVDV (post-1971) map to the first two clusters and may, by optimizing recognition of a pig CAR and/or DAF homologue, have improved the adaptation of the virus to pigs.
猪水疱病病毒（SVDV）是小RNA病毒科的一种肠道病毒，可引发与口蹄疫病毒难以区分的症状。系统发育研究表明，它是重要的人类病原体柯萨奇病毒B5（CBV5）最近进化出的一个遗传亚谱系，与此一致的是，已证明它利用柯萨奇病毒和腺病毒受体（CAR）进入细胞。UK/27/72 SVDV毒株（高毒力）的3.0埃晶体结构显示，其核心结构与其他小RNA病毒的核心结构具有预期的相似性，与最接近CBV5的可用结构——柯萨奇病毒B3（CBV3）的结构最为相似。有助于将蛋白质亚基黏合在一起并使其变硬的特征在这种病毒中有所扩展，这或许解释了它对环境因素的极强耐受性。利用大量可得的SVDV和CBV5衣壳序列，我们已将在SVDV假定适应新宿主过程中可能发生的氨基酸替换定位到SVDV的结构以及通过参考CBV3和CAR的冷冻电子显微镜可视化复合物生成的SVDV/CAR复合物模型上。这些变化分为以下三个簇：一个簇位于五重孔道周围，第二个簇映射到CAR结合位点，部分与衰变加速因子（DAF）结合埃可病毒7（ECHO7）的位点重叠，第三个簇靠近五重轴，低密度脂蛋白受体在此处与小群鼻病毒结合。SVDV后期（1971年后）的变化映射到前两个簇，可能通过优化对猪CAR和/或DAF同源物的识别，提高了病毒对猪的适应性。
