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Cardiovirus Leader proteins bind exportins: Implications for virus replication and nucleocytoplasmic trafficking

Jessica J Ciomperlik1, Holly A Basta2, Ann C Palmenberg1

  • 1Institute for Molecular Virology and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States.

Virology
|October 23, 2015
PubMed

Insights

Cardiovirus Leader proteins (LX) hijack cellular transport by recruiting exportins like Crm1 to phosphorylate nuclear pore proteins. This mechanism is crucial for viral replication and inhibiting cell trafficking.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Cardiovirus Leader proteins (LX) disrupt nucleocytoplasmic trafficking.
  • This disruption involves host kinases and nuclear pore proteins (Nups).
  • Ran GTPase interaction with LX was previously observed.

Purpose of the Study:

  • To investigate the role of exportins in the LX-mediated inhibition of nucleocytoplasmic trafficking.
  • To elucidate the mechanism of kinase recruitment and Nup phosphorylation by Cardiovirus LX proteins.

Main Methods:

  • Pull-down experiments to assess complex formation.
  • Recombinant complex reconstitution to validate interactions.
  • shRNA knockdown studies to confirm functional relevance.
  • Mutational analysis of LX protein domains.

Main Results:

  • Crm1 and CAS exportins form stable complexes with encephalomyocarditis virus LE, and with LE:Ran.
  • Similar exportin interactions were observed for Theilovirus LS and LT proteins.
  • Mutations in LX zinc finger, acidic domain, or phosphorylation sites reduced exportin selection.
  • Ran and Crm1 binding sites on LX are non-overlapping.

Conclusions:

  • Exportins are integral to the Cardiovirus LX mechanism of inhibiting nucleocytoplasmic trafficking.
  • LX proteins utilize distinct binding sites for Ran and exportins.
  • This exportin-mediated pathway is vital for viral replication.

Keywords:
CardiovirusCrm1Leader proteinNucleocytoplasmic trafficking inhibition

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