Colston E M, Racaniello V R
Department of Microbiology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
J Virol. 1995 Aug;69(8):4823-9. doi: 10.1128/JVI.69.8.4823-4829.1995.
Mutations in the predicted C'-C"-D edge of the first immunoglobulin-like domain of the poliovirus receptor were previously shown to eliminate poliovirus binding. To identify capsid residues that expand receptor recognition, 16 poliovirus suppressor mutants were selected that replicate in three different mutant receptor-expressing cell lines as well as in cells expressing the wild-type receptor. Sequence analysis of the mutant viruses revealed three capsid residues that enable poliovirus to utilize defective receptors. Two residues are in regions of the capsid that are known to regulate receptor binding and receptor-mediated conformational transitions. A third residue is located in a highly exposed loop on the virion surface that controls poliovirus host range in mice by influencing receptor recognition. One of the suppressor mutations enables the primate-restricted P1/Mahoney strain to paralyze mice by enabling the virus to recognize a receptor in the mouse central nervous system. Capsid mutations that suppress receptor defects may exert their effect at the binding site or may improve receptor binding by regulating structural transitions of the capsid.
先前的研究表明，脊髓灰质炎病毒受体第一个免疫球蛋白样结构域预测的C'-C"-D边缘的突变会消除脊髓灰质炎病毒的结合。为了确定扩展受体识别的衣壳残基，选择了16个脊髓灰质炎病毒抑制突变体，它们在三种不同的表达突变受体的细胞系以及表达野生型受体的细胞中都能复制。对突变病毒的序列分析揭示了三个衣壳残基，这些残基使脊髓灰质炎病毒能够利用有缺陷的受体。两个残基位于衣壳中已知调节受体结合和受体介导的构象转变的区域。第三个残基位于病毒粒子表面高度暴露的环上，通过影响受体识别来控制脊髓灰质炎病毒在小鼠中的宿主范围。其中一个抑制突变使灵长类动物限制型P1/马奥尼毒株能够识别小鼠中枢神经系统中的受体，从而使小鼠瘫痪。抑制受体缺陷的衣壳突变可能在结合位点发挥作用，或者通过调节衣壳的结构转变来改善受体结合。
