CRM1-Dependent Nuclear Export of Dengue Virus Type 2 NS5

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Melinda J. Pryor1,
  2. Stephen M. Rawlinson1,
  3. Peter J. Wright1,2 and
  4. David A. Jans2,3,†

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch11

New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277

New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277

How to Cite

Pryor, M. J., Rawlinson, S. M., Wright, P. J. and Jans, D. A. (2008) CRM1-Dependent Nuclear Export of Dengue Virus Type 2 NS5, in New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470058005.ch11

Author Information

  1. 1

    Department of Biochemistry and Molecular Biology, Australia

  2. 2

    Department of Microbiology Monash University, Victoria 3800, Australia

  3. 3

    Nuclear Signalling Laboratory, Department of Biochemistry & Molecular Biology, PO Box 13D, Monash University, Victoria 3800, Australia

  1. This paper was presented at the symposium by David A. Jans, to whom correspondence should be addressed.

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 25 AUG 2006

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470016435

Online ISBN: 9780470058008

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Keywords:

  • dengue;
  • flavivirus;
  • NS5;
  • importin;
  • exportin;
  • CRM1;
  • nucleus;
  • LMB;
  • leptomycin B

Summary

The dengue virus multidomain RNA polymerase NS5 has been observed in the nucleus in mammalian infected cell systems. We previously showed that NS5 nuclear localization is mediated by two nuclear targeting signals within the NS5 interdomain region that are recognized by distinct members of the importin superfamily of intracellular transporters. Intriguingly, we have recently found that NS5 also possesses the ability to be exported from the nucleus by the importin family member CRM1 (exportin 1) both in Vero cells transfected to express NS5, and in dengue virus type 2 infected Vero cells, based on use of the CRM1-specific inhibitor leptomycin B (LMB). LMB treatment of Vero cells resulted in increased nuclear accumulation in both systems, and interestingly in the latter, resulted in an alteration in the kinetics of virus production. Our results imply that subcellular trafficking of NS5 at particular times in the infectious cycle may be central to the kinetics of virus production; perturbing this trafficking may represent a viable approach to develop new antiviral therapeutics.