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Updated: Aug 30, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3'
Elena Dobrikova1, Paola Florez, Shelton Bradrick
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
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' 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.
Insights
Researchers engineered poliovirus chimeras for cancer therapy. A modified rhinovirus internal ribosomal entry site (IRES) prevents neurovirulence, enabling targeted tumor treatment without harming neurons.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Poliovirus chimeras show potential for cancer treatment.
- Neurovirulence is a significant hurdle for poliovirus-based therapies.
- Internal ribosomal entry site (IRES) elements control viral translation.
Purpose of the Study:
- To elucidate the molecular mechanism behind the cell type-specific defect caused by a heterologous rhinovirus IRES.
- To understand how this modification impacts poliovirus propagation in different cell types.
- To assess the safety and efficacy of engineered poliovirus for cancer treatment.
Main Methods:
- Construction of poliovirus chimeras with a human rhinovirus type 2 IRES.
- Assessment of viral replication and propagation in neuronal and malignant glioma cell lines.
- Analysis of viral genome structure, including 3' non-translated region interactions.
Main Results:
- The engineered poliovirus exhibited a neuron-specific propagation deficit.
- Neurovirulence was eliminated without compromising viral growth in glioma cells.
- Specific structural elements in the rhinovirus IRES and long-range RNA interactions were identified as crucial for cell-specific regulation.
Conclusions:
- The modified rhinovirus IRES effectively decouples viral replication from neurovirulence.
- This strategy offers a safer approach to poliovirus-based cancer therapy.
- Understanding IRES-RNA interactions provides insights into viral gene expression and host-pathogen interactions.
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