Crabbe M J, Evans D J, Almond J W
Department of Microbiology, School of Animal and Microbial Sciences, University of Reading, UK.
FEBS Lett. 1990 Oct 1;271(1-2):194-8. doi: 10.1016/0014-5793(90)80404-7.
We have used laboratory-based molecular modelling to identify structural features of antigen chimaeras of poliovirus expressing epitopes from human immunodeficiency virus (HIV-1) that may affect virus viability. Chimaeras were constructed by replacement of antigenic site 1 of VP1 by sequences corresponding to epitopes from HIV-1. Loop volume, estimated by approximating the loop to an ellipsoid was significantly (P less than 0.001) lower in viable (2062.1 A3 +/- 400.2) than in non-viable (3617 A3 +/- 650.7) constructs. Our results suggest that viable virus will only be formed when antigen chimeras modified at antigenic site of VP1 have a loop occupying a similar volume in space to that occupied by the antigenic site 1 loop. In addition, the modified loop must fit with the peptide bond angles and distances at the top of the beta-barrel of VP1.
我们利用基于实验室的分子建模来确定表达来自人类免疫缺陷病毒（HIV-1）表位的脊髓灰质炎病毒抗原嵌合体的结构特征，这些特征可能会影响病毒的生存能力。通过用与HIV-1表位相对应的序列替换VP1的抗原位点1来构建嵌合体。通过将环近似为椭球体来估计的环体积，在有活力的构建体（2062.1 ų ± 400.2）中显著（P小于0.001）低于无活力的构建体（3617 ų ± 650.7）。我们的结果表明，只有当在VP1抗原位点修饰的抗原嵌合体具有一个在空间中占据与抗原位点1环相似体积的环时，才会形成有活力的病毒。此外，修饰后的环必须与VP1β桶顶部的肽键角度和距离相匹配。
