Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3' nontranslated region.
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' non-translated 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.
Dobrikova
Elena
E
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Florez
Paola
P
Bradrick
Shelton
S
Gromeier
Matthias
M
D020413:3' Untranslated Regions; D001483:Base Sequence; D015153:Blotting, Western; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010849:Picornaviridae / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D011995:Recombination, Genetic; D012229:Rhinovirus / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry*; D013997:Time Factors
D020413:3' Untranslated Regions; D012313:RNA; D008156:Luciferases