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Age-dependent poliovirus replication in the mouse central nervous system is determined by internal ribosome entry

Steven Kauder1, Sherry Kan, Vincent R Racaniello

  • 1Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 W. 168th St., New York, New York 10032, USA.

Journal of Virology
|February 28, 2006
PubMed

Insights

The human rhinovirus 2 internal ribosome entry site (IRES) allows viral replication in mice, but only in young animals. This IRES function determines species specificity for HRV2 infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human rhinovirus type 2 (HRV2) does not replicate in mouse cells.
  • The internal ribosome entry site (IRES) is crucial for viral translation and replication.

Purpose of the Study:

  • To investigate the role of the HRV2 IRES in determining viral species specificity.
  • To understand the limitations of HRV2 replication in murine models.

Main Methods:

  • Constructed a recombinant poliovirus (P1/HRV2) with the HRV2 IRES.
  • Assessed viral replication in human and murine cell lines.
  • Inoculated transgenic mice (expressing poliovirus receptor CD155) with P1/HRV2.
  • Used recombinant adenoviruses to study IRES-mediated translation in murine organs.

Main Results:

  • The HRV2 IRES enabled P1/HRV2 replication in both human and murine cell lines.
  • P1/HRV2 replicated in the central nervous system of neonatal but not adult transgenic mice.
  • HRV2 IRES-mediated translation occurred in neonatal but not adult murine organs.
  • Passage in mice selected for a virulent HRV2 strain causing paralysis.

Conclusions:

  • The HRV2 IRES is not inherently limited by murine cells but its function is age-dependent.
  • HRV2 IRES-mediated translation is a key determinant of viral replication in the murine central nervous system.
  • The IRES dictates the species specificity of HRV2 infection.

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