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Activity of a Type 1 Picornavirus Internal Ribosomal Entry Site Is Determined by Sequences within the 3′ Nontranslated Region

Elena Dobrikova, Paola Florez, Shelton Bradrick and Matthias Gromeier
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 25 (Dec. 9, 2003), pp. 15125-15130
Stable URL: http://www.jstor.org/stable/3148571
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Activity of a Type 1 Picornavirus Internal Ribosomal Entry Site Is Determined by Sequences within the 3′ Nontranslated Region
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Abstract

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.

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