Moss E G, Racaniello V R
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
EMBO J. 1991 May;10(5):1067-74. doi: 10.1002/j.1460-2075.1991.tb08046.x.
The inability of certain poliovirus strains to infect mice can be overcome by the expression of human poliovirus receptors in mice or by the presence of a particular amino acid sequence of the B-C loop of the viral capsid protein VP1. We have identified changes in an additional capsid structure that permit host-restricted poliovirus strains to infect mice. Variants of the mouse-virulent P2/Lansing strain were constructed containing amino acid changes, deletions and insertions in the B-C loop of VP1. These variants were attenuated in mice, demonstrating the importance of the B-C loop sequence in host range. Passage of two of the B-C loop variants in mice led to the selection of viruses that were substantially more virulent. The increased neurovirulence of these strains was mapped to two different suppressor mutations in the N-terminus of VP1. Whereas the B-C loop of VP1 is highly exposed on the surface of the capsid, near the five-fold axis of symmetry, the suppressor mutations are in the interior of the virion, near the three-fold axis. Introduction of the suppressor mutations into the genome of the mouse-avirulent P1/Mahoney strain resulted in neurovirulent viruses, demonstrating that the P2/Lansing B-C loop sequence is not required to infect mice. Because the internal host range determinants are in a structure known to be important in conformational transitions of the virion, the host range of poliovirus may be determined by the ability of virions to undergo transitions catalyzed by cell receptors.
某些脊髓灰质炎病毒株无法感染小鼠的情况可通过在小鼠中表达人脊髓灰质炎病毒受体或病毒衣壳蛋白VP1的B - C环特定氨基酸序列的存在来克服。我们已经确定了另一种衣壳结构中的变化，这些变化使宿主受限的脊髓灰质炎病毒株能够感染小鼠。构建了小鼠强毒株P2/Lansing株的变体，其VP1的B - C环中含有氨基酸变化、缺失和插入。这些变体在小鼠中减毒，证明了B - C环序列在宿主范围中的重要性。两种B - C环变体在小鼠中传代导致选择出毒性更强的病毒。这些毒株神经毒性增加被定位到VP1 N端的两个不同的抑制突变。虽然VP1的B - C环高度暴露在衣壳表面，靠近五重对称轴，但抑制突变位于病毒粒子内部，靠近三重轴。将抑制突变引入小鼠无毒株P1/Mahoney的基因组中产生了神经毒性病毒，表明感染小鼠不需要P2/Lansing的B - C环序列。由于内部宿主范围决定因素存在于已知在病毒粒子构象转变中起重要作用的结构中，脊髓灰质炎病毒的宿主范围可能由病毒粒子经历细胞受体催化的转变的能力决定。
