This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Macdonald, J.
Right arrow Articles by Lipkin, W. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Macdonald, J.
Right arrow Articles by Lipkin, W. I.

 Previous Article  |  Next Article 

Journal of Virology, November 2005, p. 13924-13933, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13924-13933.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

NS1 Protein Secretion during the Acute Phase of West Nile Virus Infection

Joanne Macdonald,1 Jessica Tonry,2 Roy A. Hall,3 Brent Williams,1 Gustavo Palacios,1 Mundrigi S. Ashok,1 Omar Jabado,1 David Clark,3 Robert B. Tesh,2 Thomas Briese,1 and W. Ian Lipkin1*

Jerome L. and Dawn Greene Infectious Disease Laboratory, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York,1 Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas,2 Department of Microbiology and Parasitology, School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Australia3

Received 4 February 2005/ Accepted 21 July 2005

The West Nile virus (WNV) nonstructural protein NS1 is a protein of unknown function that is found within, associated with, and secreted from infected cells. We systematically investigated the kinetics of NS1 secretion in vitro and in vivo to determine the potential use of this protein as a diagnostic marker and to analyze NS1 secretion in relation to the infection cycle. A sensitive antigen capture enzyme-linked immunosorbent assay (ELISA) for detection of WNV NS1 (polyclonal-ACE) was developed, as well as a capture ELISA for the specific detection of NS1 multimers (4G4-ACE). The 4G4-ACE detected native NS1 antigens at high sensitivity, whereas the polyclonal-ACE had a higher specificity for recombinant forms of the protein. Applying these assays we found that only a small fraction of intracellular NS1 is secreted and that secretion of NS1 in tissue culture is delayed compared to the release of virus particles. In experimentally infected hamsters, NS1 was detected in the serum between days 3 and 8 postinfection, peaking on day 5, the day prior to the onset of clinical disease; immunoglobulin M (IgM) antibodies were detected at low levels on day 5 postinfection. Although real-time PCR gave the earliest indication of infection (day 1), the diagnostic performance of the 4G4-ACE was comparable to that of real-time PCR during the time period when NS1 was secreted. Moreover, the 4G4-ACE was found to be superior in performance to both the IgM and plaque assays during this time period, suggesting that NS1 is a viable early diagnostic marker of WNV infection.

* Corresponding author. Mailing address: Jerome L. and Dawn Greene Infectious Disease Laboratory, Departments of Epidemiology, Neurology and Pathology, Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, 722 W. 168th St, Rm. 1801, New York, NY 10032. Phone: (212) 342-9031. Fax: (212) 342-9044. E-mail: wil2001{at}columbia.edu.

Journal of Virology, November 2005, p. 13924-13933, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13924-13933.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schweitzer, B. K., Chapman, N. M., Iwen, P. C. (2009). Overview of the Flaviviridae With an Emphasis on the Japanese Encephalitis Group Viruses. Lab Med 40: 493-499 [Abstract] [Full Text]  
  • Krishna, V. D., Rangappa, M., Satchidanandam, V. (2009). Virus-Specific Cytolytic Antibodies to Nonstructural Protein 1 of Japanese Encephalitis Virus Effect Reduction of Virus Output from Infected Cells. J. Virol. 83: 4766-4777 [Abstract] [Full Text]  
  • Wilson, J. R., de Sessions, P. F., Leon, M. A., Scholle, F. (2008). West Nile Virus Nonstructural Protein 1 Inhibits TLR3 Signal Transduction. J. Virol. 82: 8262-8271 [Abstract] [Full Text]  
  • Noueiry, A. O., Olivo, P. D., Slomczynska, U., Zhou, Y., Buscher, B., Geiss, B., Engle, M., Roth, R. M., Chung, K. M., Samuel, M., Diamond, M. S. (2007). Identification of Novel Small-Molecule Inhibitors of West Nile Virus Infection. J. Virol. 81: 11992-12004 [Abstract] [Full Text]  
  • Clark, D. C., Lobigs, M., Lee, E., Howard, M. J., Clark, K., Blitvich, B. J., Hall, R. A. (2007). In situ reactions of monoclonal antibodies with a viable mutant of Murray Valley encephalitis virus reveal an absence of dimeric NS1 protein. J. Gen. Virol. 88: 1175-1183 [Abstract] [Full Text]  
  • Schaecher, S. R., Mackenzie, J. M., Pekosz, A. (2007). The ORF7b Protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Is Expressed in Virus-Infected Cells and Incorporated into SARS-CoV Particles. J. Virol. 81: 718-731 [Abstract] [Full Text]  
  • Chung, K. M., Liszewski, M. K., Nybakken, G., Davis, A. E., Townsend, R. R., Fremont, D. H., Atkinson, J. P., Diamond, M. S. (2006). From the Cover: West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Proc. Natl. Acad. Sci. USA 103: 19111-19116 [Abstract] [Full Text]  
  • Schlesinger, J. J. (2006). Flavivirus nonstructural protein NS1: Complementary surprises. Proc. Natl. Acad. Sci. USA 103: 18879-18880 [Full Text]  
  • Samuel, M. A., Diamond, M. S. (2006). Pathogenesis of West Nile Virus Infection: a Balance between Virulence, Innate and Adaptive Immunity, and Viral Evasion. J. Virol. 80: 9349-9360 [Full Text]  
  • Chung, K. M., Nybakken, G. E., Thompson, B. S., Engle, M. J., Marri, A., Fremont, D. H., Diamond, M. S. (2006). Antibodies against West Nile Virus Nonstructural Protein NS1 Prevent Lethal Infection through Fc {gamma} Receptor-Dependent and -Independent Mechanisms. J. Virol. 80: 1340-1351 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»