A Genomics Approach to Understanding Host Response during Dengue Infection

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Martin L. Hibberd1,2,
  2. Ling Ling1,
  3. Thomas Tolfvenstam1,
  4. Wayne Mitchell1,
  5. Chris Wong1,
  6. Vladimir A. Kuznetsov1,
  7. Joshy George1,
  8. Swee-Hoe Ong1,
  9. Yijun Ruan1,
  10. Chia L. Wei1,
  11. Feng Gu3,
  12. Joshua Fink3,
  13. Andy Yip3,
  14. Wei Liu3,
  15. Mark Schreiber3 and
  16. Subhash G. Vasudevan3

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch15

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

Hibberd, M. L., Ling, L., Tolfvenstam, T., Mitchell, W., Wong, C., Kuznetsov, V. A., George, J., Ong, S.-H., Ruan, Y., Wei, C. L., Gu, F., Fink, J., Yip, A., Liu, W., Schreiber, M. and Vasudevan, S. G. (2006) A Genomics Approach to Understanding Host Response during Dengue Infection, 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.ch15

Author Information

  1. 1

    Genome Institute of Singapore, Biopolis, Singapore 138670

  2. 2

    Population Genetics (Infectious Disease), Genome Institute of Singapore, Genome #02-01, 60 Biopolis Street, Singapore 138672

  3. 3

    Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos #05-01, Singapore 138670

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:

  • genomic approach to host defence;
  • SARS coronavirus genetic diversity tracking;
  • dengue virus variation determining host response;
  • high-density custom microarrays;
  • dengue resequencing cost-effective mechanism

Summary

Dengue infection results in a wide clinical spectrum, ranging from asymptomatic, through fever (DF), to the life threatening complications haemorrhagic fever (DHF) and shock syndrome (DSS). Although we now understand that factors such as repeat infections and the type or magnitude of the host response are important in determining severity, the mechanisms of these actions remain largely unknown. Understanding this host–pathogen interaction may enable outcome prediction and new therapy options. Developments in biology now allow a ‘systems approach’ to be applied to this problem, utilizing whole genomes of both human and virus, in vitro and in vivo to enable a more complete picture of their interplay to be built up. We have developed a chip-based approach to viral sequencing, to increase efficiency and enable large numbers of genomes to be completed, together with a web-based interpretation tool. We have also applied human whole genome expression arrays (24 000 genes) to characterize the types of host response made to infection and plan to investigate the role of host variation using human whole genome genetic association studies in the future. These technologies have identified novel host pathways involved in viral replication in vitro, and also host immune responses, such as the interferon signalling pathway, that are influenced by viral sequence. This data will be further refined through interlinking with similar data obtained from a large study of dengue patients, initiated in Singapore, that is able to look at the early host response to infection.