Secretion of Flaviviral Non-Structural Protein NS1: from Diagnosis to Pathogenesis

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. S. Alcon-LePoder1,†,
  2. P. Sivard1,
  3. M.-T. Drouet1,
  4. A. Talarmin2,
  5. C. Rice Chair3 and
  6. M. Flamand1,3,‡

Published Online: 7 OCT 2008

DOI: 10.1002/0470058005.ch17

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

Alcon-LePoder, S., Sivard, P., Drouet, M.-T., Talarmin, A., Rice, C. and Flamand, M. (2008) Secretion of Flaviviral Non-Structural Protein NS1: from Diagnosis to Pathogenesis, 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.ch17

Author Information

  1. 1

    Institut Pasteur, Virology Department, 25 Rue du Dr Roux, 75015 Paris, France

  2. 2

    Institut Pasteur Madagascar, BP 1274, Antananarivo 101, Madagascar

  3. 3

    Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, Box 64, New York, NY 10021, USA

  1. Present address: ENVA, 7 avenue du Général de Gaulle, 94704 Maisons-Alfort Cedex, France.

  2. This paper was presented at the symposium by M. Flamand, 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:

  • Flavivirus;
  • dengue;
  • yellow fever;
  • West Nile;
  • non-structural;
  • glycoprotein;
  • secretion;
  • diagnosis;
  • viral pathogenesis

Summary

Flaviviruses are major arthropod-borne human pathogens responsible for lifethreatening encephalitis, hepatitis and haemorrhagic fevers. These enveloped, singlestranded, positive-sense RNA viruses encode a polyprotein precursor of about 3400 amino acids, processed into three structural and seven non-structural proteins. The non-structural glycoprotein NS1 is essential for flavivirus viability. During host-cell infection in vitro, NS1 is found associated with intracellular organelles as a requisite for its role in viral replication, or is transported to the cell surface where it may trigger specific signalling pathways. In addition, a secreted form of the protein is released from flavivirus-infected mammalian cells. We have previously shown that the NS1 protein circulates during the acute phase of the disease in the plasma of patients infected with dengue virus type 1 and have extended our retrospective studies to dengue type 2 and type 3 cohorts, confirming the value of the NS1 antigen as an alternative diagnostic marker. Interestingly, detection of the NS1 protein in yellow fever virus and West Nile virus infections suggests that NS1 secretion is a hallmark of human flavivirus infections. The objectives of our current studies are to define the biological properties of the secreted form of the NS1 protein, to evaluate its possible contribution to viral pathogenesis, and to validate this protein as a candidate target for passive immunoprophylaxis against flaviviruses.