Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region

被引:51
作者
Dobrikova, E [1 ]
Florez, P [1 ]
Bradrick, S [1 ]
Gromeier, M [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
关键词
D O I
10.1073/pnas.2436464100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. We now report the elucidation of a molecular mechanism responsible for the cell type-specific defect mediated by the rhinovirus IRES. Rhinovirus IRES function in neuronal cell types depends on specific structural elements within the 3' nontranslated region of the viral genome. Our observations suggest long-range interactions between the IRES and the 3' terminus that control IRES-mediated gene expression and virus propagation.
引用
收藏
页码:15125 / 15130
页数:6
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