Cardiovirus 2A protein associates with 40S but not 80S ribosome subunits during infection

Rachel Groppo1, Ann C Palmenberg

  • 1Department of Biochemistry, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, USA.

Journal of Virology
|August 31, 2007
PubMed

Insights

Encephalomyocarditis virus (EMCV) inhibits host cell translation by reducing mRNA on ribosomes. Viral protein 2A is key to this shutoff mechanism in cardiovirus infections.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Picornaviruses inhibit host cell translation, but mechanisms vary by genus.
  • Encephalomyocarditis virus (EMCV), a cardiovirus, is known to induce host translation shutoff.

Purpose of the Study:

  • To investigate alterations in cellular translational machinery in HeLa cells infected with EMCV.
  • To elucidate the role of viral protein 2A in cardiovirus-induced host translational shutoff.

Main Methods:

  • Infection of HeLa cells with EMCV.
  • Analysis of cellular translational components, including mRNA, ribosomes, and polysomes.
  • Characterization of viral protein 2A association with ribosomal subunits.
  • Reporter assays to assess translation efficiency.

Main Results:

  • EMCV infection significantly decreased host mRNA translation, correlating with increased 80S ribosome peaks and decreased polysomes.
  • Accumulated 80S ribosomes were largely devoid of mRNA.
  • Viral protein 2A was associated with 40S subunits but not the 80S pool.
  • Exogenous expression of 2A protein shifted translation towards internal ribosome entry site (IRES)-dependent pathways.

Conclusions:

  • Viral protein 2A plays a crucial role in cardiovirus-induced host translational shutoff.
  • EMCV's shutoff mechanism involves the disruption of mRNA binding to ribosomes.
  • The findings provide a deeper understanding of picornavirus strategies to subvert host cell machinery.

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