NS1 protein secretion during the acute phase of West Nile virus infection

Joanne Macdonald, Jessica Tonry, Roy A. Hall, Brent Williams, Gustavo Palacios, Mundrigi S. Ashok, Omar Jabado, David Clark, Robert B. Tesh, Thomas Briese, W. Ian Lipkin

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13924-13933
Number of pages10
JournalJournal of Virology
Volume79
Issue number22
DOIs
StatePublished - Nov 2005

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West Nile virus
protein secretion
Virus Diseases
Immunoglobulin M
Real-Time Polymerase Chain Reaction
Enzyme-Linked Immunosorbent Assay
Antigens
immunoglobulin M
secretion
Infection
Recombinant Proteins
Cricetinae
infection
Virion
quantitative polymerase chain reaction
Proteins
proteins
enzyme-linked immunosorbent assay
antigens
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Macdonald, J., Tonry, J., Hall, R. A., Williams, B., Palacios, G., Ashok, M. S., ... Lipkin, W. I. (2005). NS1 protein secretion during the acute phase of West Nile virus infection. Journal of Virology, 79(22), 13924-13933. https://doi.org/10.1128/JVI.79.22.13924-13933.2005

NS1 protein secretion during the acute phase of West Nile virus infection. / Macdonald, Joanne; Tonry, Jessica; Hall, Roy A.; Williams, Brent; Palacios, Gustavo; Ashok, Mundrigi S.; Jabado, Omar; Clark, David; Tesh, Robert B.; Briese, Thomas; Lipkin, W. Ian.

In: Journal of Virology, Vol. 79, No. 22, 11.2005, p. 13924-13933.

Research output: Contribution to journalArticle

Macdonald, J, Tonry, J, Hall, RA, Williams, B, Palacios, G, Ashok, MS, Jabado, O, Clark, D, Tesh, RB, Briese, T & Lipkin, WI 2005, 'NS1 protein secretion during the acute phase of West Nile virus infection', Journal of Virology, vol. 79, no. 22, pp. 13924-13933. https://doi.org/10.1128/JVI.79.22.13924-13933.2005
Macdonald J, Tonry J, Hall RA, Williams B, Palacios G, Ashok MS et al. NS1 protein secretion during the acute phase of West Nile virus infection. Journal of Virology. 2005 Nov;79(22):13924-13933. https://doi.org/10.1128/JVI.79.22.13924-13933.2005
Macdonald, Joanne ; Tonry, Jessica ; Hall, Roy A. ; Williams, Brent ; Palacios, Gustavo ; Ashok, Mundrigi S. ; Jabado, Omar ; Clark, David ; Tesh, Robert B. ; Briese, Thomas ; Lipkin, W. Ian. / NS1 protein secretion during the acute phase of West Nile virus infection. In: Journal of Virology. 2005 ; Vol. 79, No. 22. pp. 13924-13933.
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