Dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence
Dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence
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DOI：
10.1128/jvi.73.2.958-964.1999
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发表时间：
1999-02-01
影响因子：
5.4
通讯作者：
Wimmer, E
中科院分区：
文献类型：
--
作者：
Gromeier, M;Bossert, B;Wimmer, E
在人类中枢神经系统中，对脊髓灰质炎病毒（PV）感染的易感性很大程度上局限于神经元细胞的特定亚群。 PV 向性可能由细胞外部成分（例如 PV 受体 CD155）以及细胞内部限制（例如是否有适合病毒繁殖的微环境）决定。我们之前报道过，PV 5'非翻译区内的同源内部核糖体进入位点（IRES）与其来自人鼻病毒2型（HRV2）的对应位点的交换可以消除脊髓灰质炎转基因小鼠模型中的神经致病表型，而不削弱HeLa细胞的生长特性。我们现在表明，PV/HRV2 嵌合体的神经毒力减弱不仅限于 CD155 转基因小鼠，而且在食蟹猴脊柱内接种后也很明显。我们已经剖析了 PV 和 HRV2 IRES 元件，以确定负责这些嵌合病毒神经毒力（或减毒）的结构。我们报告了 IRES 内两个相邻的茎环结构共同决定神经致病性。
In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5' nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity.