Couderc T, Delpeyroux F, Le Blay H, Blondel B
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, Paris, France.
J Virol. 1996 Jan;70(1):305-12. doi: 10.1128/JVI.70.1.305-312.1996.
Most poliovirus (PV) strains, such as PV type 1/Mahoney, cannot infect the mouse central nervous system. We previously identified two determinants of mouse adaptation of PV type 1/Mahoney at positions 22 and 31 of the viral capsid proteins VP1 and VP2, respectively (T. Couderc, J. Hogle, H. Le Blay, F. Horaud, and B. Blondel, J. Virol. 67:3808-3817, 1993). These residues are located on the interior surface of the capsid. In an attempt to understand the molecular mechanisms of adaptation of PV to mice, we investigated the effects of these two determinants on the viral multiplication cycle in a human cell line. Both determinants enhanced receptor-mediated conformational changes leading to altered particles of 135S, one of the first steps of uncoating, and viral internalization. Furthermore, the residue at position 22 of VP1 appears to facilitate RNA release. These results strongly suggest that these determinants could also facilitate conformational changes mediated by the PV murine receptor and internalization in the mouse nerve cell, thus allowing PV to overcome its host range restriction. Moreover, both mouse adaptation determinants are responsible for defects in the assembly of virions in human cells and affect the thermostability of the viral particles. Thus, these mouse adaptation determinants appear to control the balance between the viral capsid plasticity needed for the conformational changes in the early steps of infection and the structural requirements which are involved in the assembly and the stability of virions.
大多数脊髓灰质炎病毒（PV）毒株，如1型PV/Mahoney，无法感染小鼠中枢神经系统。我们之前分别在病毒衣壳蛋白VP1和VP2的第22位和第31位鉴定出了1型PV/Mahoney适应小鼠的两个决定因素（T.库德克、J.霍格尔、H.勒布莱、F.奥罗和B.布隆代尔，《病毒学杂志》67:3808 - 3817，1993年）。这些残基位于衣壳的内表面。为了试图理解PV适应小鼠的分子机制，我们研究了这两个决定因素对人细胞系中病毒增殖周期的影响。这两个决定因素均增强了受体介导的构象变化，导致脱衣的第一步——135S颗粒改变以及病毒内化。此外，VP1第22位的残基似乎有助于RNA释放。这些结果有力地表明，这些决定因素也可能促进由PV小鼠受体介导的构象变化以及在小鼠神经细胞中的内化，从而使PV克服其宿主范围限制。此外，这两个小鼠适应决定因素均导致人细胞中病毒粒子组装缺陷，并影响病毒颗粒的热稳定性。因此，这些小鼠适应决定因素似乎控制着感染早期步骤中构象变化所需的病毒衣壳可塑性与病毒粒子组装和稳定性所涉及的结构要求之间的平衡。
