Structural and Functional Analysis of Dengue Virus RNA

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Diego E. Alvarez,
  2. Maria F. Lodeiro,
  3. Claudia V. Filomatori,
  4. Silvana Fucito,
  5. Juan A. Mondotte and
  6. Andrea V. Gamarnik

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch9

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

Alvarez, D. E., Lodeiro, M. F., Filomatori, C. V., Fucito, S., Mondotte, J. A. and Gamarnik, A. V. (2008) Structural and Functional Analysis of Dengue Virus RNA, 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.ch9

Author Information

  1. Fundación Instituto Leloir, Patricias Argentinas 435, Buenos Aires 1405, Argentina

  1. This paper was presented at the symposium by Andrea Gamarnik, 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 virus;
  • flavivirus;
  • RNA cyclization;
  • RNA synthesis;
  • RNA-RNA interactions;
  • AFM;
  • viral replicon;
  • viral translation

Summary

Sequences and structures present at the 5′ and 3′ UTRs of RNA viruses play crucial roles in the initiation and regulation of translation, RNA synthesis and viral assembly. In dengue virus, as well as in other mosquito-borne flaviviruses, the presence of complementary sequences at the ends of the genome mediate long-range RNA–RNA interactions. Dengue virus RNA displays two pairs of complementary sequences (CS and UAR) required for genome circularization and viral viability. In order to study the molecular mechanism by which these RNA–RNA interactions participate in the viral life cycle, we developed a dengue virus replicon system. RNA transfection of the replicon in mosquito and mammalian cells allows discrimination between RNA elements involved in translation and RNA synthesis. We found that mutations within CS or UAR at the 5′ or 3′ ends of the RNA that interfere with base pairing did not significantly affect translation of the input RNA but seriously compromised or abolished RNA synthesis. Furthermore, a systematic mutational analysis of UAR sequences indicated that, beside the role in RNA cyclization, specific nucleotides within UAR are also important for efficient RNA synthesis.