Shiroki K, Ishii T, Aoki T, Ota Y, Yang W X, Komatsu T, Ami Y, Arita M, Abe S, Hashizume S, Nomoto A
Department of Microbiology, Institute of Medical Science, University of Tokyo, Minatoku, Japan.
J Virol. 1997 Jan;71(1):1-8. doi: 10.1128/JVI.71.1.1-8.1997.
Most poliovirus strains infect only primates. The host range (HR) of poliovirus is thought to be primarily determined by a cell surface molecule that functions as poliovirus receptor (PVR), since it has been shown that transgenic mice are made poliovirus sensitive by introducing the human PVR gene into the genome. The relative levels of neurovirulence of polioviruses tested in these transgenic mice were shown to correlate well with the levels tested in monkeys (H. Horie et al., J. Virol. 68:681-688, 1994). Mutants of the virulent Mahoney strain of poliovirus have been generated by disruption of nucleotides 128 to 134, at stem-loop II within the 5' noncoding region, and four of these mutants multiplicated well in human HeLa cells but poorly in mouse TgSVA cells that had been established from the kidney of the poliovirus-sensitive transgenic mouse. Neurovirulence tests using the two animal models revealed that these mutants were strongly attenuated only in tests with the mouse model and were therefore HR mutants. The virus infection cycle in TgSVA cells was restricted by an internal ribosomal entry site (IRES)-dependent initiation process of translation. Viral protein synthesis and the associated block of cellular protein synthesis were not observed in TgSVA cells infected with three of four HR mutants and was evident at only a low level in the remaining mutant. The mutant RNAs were functional in a cell-free protein synthesis system from HeLa cells but not in those from TgSVA and mouse neuroblastoma NS20Y cells. These results suggest that host factor(s) affecting IRES-dependent translation of poliovirus differ between human and mouse cells and that the mutant IRES constructs detect species differences in such host factor(s). The IRES could potentially be a host range determinant for poliovirus infection.
大多数脊髓灰质炎病毒株仅感染灵长类动物。脊髓灰质炎病毒的宿主范围（HR）被认为主要由一种作为脊髓灰质炎病毒受体（PVR）的细胞表面分子决定，因为已有研究表明，通过将人类PVR基因导入基因组，可使转基因小鼠对脊髓灰质炎病毒敏感。在这些转基因小鼠中测试的脊髓灰质炎病毒的神经毒力相对水平与在猴子中测试的水平高度相关（H. Horie等人，《病毒学杂志》68:681 - 688，1994年）。通过破坏5'非编码区内茎环II处的核苷酸128至134，产生了脊髓灰质炎病毒强毒株Mahoney的突变体，其中四个突变体在人HeLa细胞中增殖良好，但在从脊髓灰质炎病毒敏感转基因小鼠肾脏建立的小鼠TgSVA细胞中增殖较差。使用这两种动物模型进行的神经毒力测试表明，这些突变体仅在小鼠模型测试中表现出强烈的减毒，因此是宿主范围突变体。TgSVA细胞中的病毒感染周期受到内部核糖体进入位点（IRES）依赖性翻译起始过程的限制。在感染四个HR突变体中的三个的TgSVA细胞中未观察到病毒蛋白合成以及相关的细胞蛋白合成阻滞，而在其余突变体中仅在低水平上明显。突变体RNA在来自HeLa细胞的无细胞蛋白质合成系统中具有功能，但在来自TgSVA和小鼠神经母细胞瘤NS20Y细胞的系统中则没有。这些结果表明，影响脊髓灰质炎病毒IRES依赖性翻译的宿主因子在人和小鼠细胞之间存在差异，并且突变的IRES构建体检测到了此类宿主因子的物种差异。IRES可能是脊髓灰质炎病毒感染的宿主范围决定因素。
