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Translation without eIF2 promoted by poliovirus 2A protease.
Natalia Redondo1, Miguel Angel Sanz, Ewelina Welnowska
1Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain. nsevillano@cbm.uam.es
Plos One
|October 18, 2011
Summary
Poliovirus translation uses a dual mechanism for protein synthesis initiation. The viral protease 2A(pro) enables eIF2-independent translation, crucial for late-stage infection.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Picornaviruses, including poliovirus, are RNA viruses that infect host cells.
- Translation initiation in eukaryotes typically requires the eukaryotic initiation factor 2 (eIF2).
- Picornavirus RNA translation is known to utilize internal ribosome entry site (IRES) elements.
Purpose of the Study:
- To investigate the mechanism of poliovirus translation initiation during infection.
- To determine the role of eIF2 and viral proteins in poliovirus RNA translation.
- To elucidate the dual mechanism of translation initiation employed by poliovirus.
Main Methods:
- Cell-free translation systems.
- Analysis of poliovirus non-structural proteins, specifically 2A(pro).
- Infection of culture cells and assessment of protein synthesis.
Main Results:
- Poliovirus translation occurs at late infection times when eIF2 is phosphorylated and inactivated.
- The viral protease 2A(pro) is sufficient to confer eIF2 independence for IRES-driven translation.
- High levels of 2A(pro) are necessary for eIF2 independence, and this function requires 2A(pro)'s ability to cleave eIF4G.
Conclusions:
- Poliovirus employs a dual mechanism for translation initiation, adapting to host cell conditions.
- Viral protease 2A(pro) plays a key role in overcoming eIF2 inactivation, enabling viral protein synthesis.
- This discovery opens new research avenues in picornavirus protein synthesis and host-pathogen interactions.
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