Macadam A J, Pollard S R, Ferguson G, Skuce R, Wood D, Almond J W, Minor P D
National Institute for Biological Standards and Control, Potters Bar, Herts, United Kingdom.
Virology. 1993 Jan;192(1):18-26. doi: 10.1006/viro.1993.1003.
The type 2 live-attenuated vaccine strain of poliovirus (P2/Sabin) is associated with rare cases of poliomyelitis in vaccinees or their contacts. Recombinants were generated between infectious clones of a neurovirulent isolate from one such case (P2/117) and P2/Sabin and neurovirulence assays suggested that a maximum of six nucleotide differences between the two strains were responsible for their phenotypic difference. Site-directed mutagenesis of P2/Sabin showed that mutations at just two positions, at 481 in the 5' non-coding region and at VP1-143 in the capsid proteins, resulted in a highly neurovirulent virus. Other nucleotide changes may have weaker phenotypic effects. These results are consistent with those reported in the mouse model by Ren et al. [J. Virol. 65, 1377, (1991)] indicating that, for P2/Sabin at least, the same determinants of attenuation are important in both primates and transgenic mice expressing the poliovirus receptor. Sequence analysis of isolates from other vaccine-associated cases of poliomyelitis and from healthy vaccinees showed that both major determinants of attenuation are unstable on human passage, although selection pressures against an A at 481 are stronger than those against an Ile at 1143.
脊髓灰质炎病毒2型减毒活疫苗株（P2/萨宾株）与疫苗接种者或其接触者中罕见的脊髓灰质炎病例有关。从一例此类病例（P2/117）的神经毒力分离株的感染性克隆与P2/萨宾株之间产生了重组体，神经毒力测定表明，这两种毒株之间最多六个核苷酸差异导致了它们的表型差异。对P2/萨宾株进行定点诱变表明，仅5'非编码区481位和衣壳蛋白VP1-143位的两个位置发生突变，就会产生一种高度神经毒力的病毒。其他核苷酸变化可能具有较弱的表型效应。这些结果与Ren等人在小鼠模型中报道的结果一致[《病毒学杂志》65, 1377, (1991)]，表明至少对于P2/萨宾株而言，在表达脊髓灰质炎病毒受体的灵长类动物和转基因小鼠中，相同的减毒决定因素都很重要。对其他疫苗相关脊髓灰质炎病例和健康疫苗接种者分离株的序列分析表明，尽管针对481位A的选择压力比对1143位异亮氨酸的选择压力更强，但两个主要减毒决定因素在人传代过程中都是不稳定的。
