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Cell-dependent role for the poliovirus 3' noncoding region in positive-strand RNA synthesis

David M Brown1, Steven E Kauder, Christopher T Cornell

  • 1Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697, USA.

Journal of Virology
|January 15, 2004
PubMed

Insights

Poliovirus RNA replication requires its 3' noncoding region, especially in neuronal cells. This region is crucial for positive-strand RNA synthesis and viral neurovirulence.

Area of Science:

  • Virology
  • Molecular Biology
  • Neuroscience

Background:

  • Poliovirus RNA replication is essential for viral propagation.
  • The 3' noncoding region of poliovirus genomic RNA plays a role in replication.
  • Previous studies showed a minor defect in viral RNA replication with a 3' noncoding region deletion mutant.

Purpose of the Study:

  • To investigate the role of the poliovirus genomic 3' noncoding region in viral RNA replication.
  • To analyze the impact of this deletion on viral growth in neuronal cells.
  • To determine the effect on viral neurovirulence.

Main Methods:

  • Infection of HeLa and SK-N-SH cells with a poliovirus mutant lacking the 3' noncoding region.
  • Analysis of viral RNA replication and synthesis.
  • Assessment of viral translation and protein processing.
  • Neurovirulence testing in transgenic mice expressing the human poliovirus receptor.

Main Results:

  • A deletion mutant lacking the poliovirus 3' noncoding region showed a minor replication defect in HeLa cells.
  • This defect was significantly exacerbated in SK-N-SH neuronal cells, leading to reduced mutant virus growth.
  • The deletion resulted in a defect in positive-strand RNA synthesis, not viral translation or protein processing.
  • The mutant virus required over 1,000-fold higher doses to paralyze mice compared to wild-type virus.

Conclusions:

  • The poliovirus 3' noncoding region is critical for positive-strand RNA synthesis during genome replication.
  • Neuronal cells may have limiting cellular factors that interact with the 3' noncoding region.
  • The 3' noncoding region contributes to poliovirus neurovirulence.

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