Molecular Biology of Flaviviruses

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Eva Harris,
  2. Katherine L. Holden,
  3. Dianna Edgil,
  4. Charlotta Polacek and
  5. Karen Clyde

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch3

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

Harris, E., Holden, K. L., Edgil, D., Polacek, C. and Clyde, K. (2006) Molecular Biology of Flaviviruses, 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.ch3

Author Information

  1. Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 140 Warren Hall, Berkeley, California 94720-7360, USA

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:

  • flavivirus dengue virus (DENV);
  • flavivirus molecular biology;
  • peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMOs);
  • flaviviral genome interaction in RNA genome replication;
  • genomic RNA in RNA synthesis and viral replication

Summary

Flaviviruses are enveloped viruses with a single-stranded, 10.7 kb positivesense RNA genome. The genomic RNA, which has a 5′ cap but no poly(A) tail, is translated as a single polyprotein that is then cleaved into three structural proteins and seven non-structural (NS) proteins by both viral and host proteases. The NS proteins include an RNA-dependent RNA polymerase (NS5), a helicase/protease (NS3), and other proteins that form part of the viral replication complex. Sequences and structures in the 5′ and 3′ untranslated regions (UTR) and capsid gene, including the cyclization sequences, the upstream AUG region, and the terminal 3′ stem-loop, regulate translation, RNA synthesis and viral replication. We have also found that an RNA hairpin structure in the capsid coding region (cHP) influences start codon selection and viral replication of the flavivirus dengue virus (DENV). Peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMOs) were used to further dissect the role of conserved regions of the 5′ and 3′ UTRs; several P-PMOs were shown to specifically inhibit DENV translation and/or RNA synthesis and, hence, are potentially useful as antiviral agents. Regarding the mechanism of DENV translation, we have shown that DENV undergoes canonical cap-dependent translation initiation as well as a non-canonical mechanism when cap-dependent translation is suppressed. Although much remains to be elucidated about the molecular biology of flavivirus infection, progress is being made towards defining the cis and trans factors that regulate flavivirus translation and replication.