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 and Lipkin, W. Ian (2005) NS1 protein secretion during the acute phase of West Nile virus infection. Journal of Virology, 79 22: 13924-13933. doi:10.1128/JVI.79.22.13924-13933.2005

Author 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
Title NS1 protein secretion during the acute phase of West Nile virus infection
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2005-11
Year available 2005
Sub-type Article (original research)
DOI 10.1128/JVI.79.22.13924-13933.2005
Open Access Status DOI
Volume 79
Issue 22
Start page 13924
End page 13933
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2005
Language eng
Subject C1
270303 Virology
270304 Infectious Agents
270802 Diagnostic Applications
730305 Diagnostic methods
780105 Biological sciences
730101 Infectious diseases
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 WNW 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.
Keyword Virology
Japanese Encephalitis-virus
Nonstructural Glycoprotein Ns1
Complement-fixing Antigen
Capture Enzyme-immunoassay
Field-collected Mosquitos
Rna Replication
Q-Index Code C1
Institutional Status UQ

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Created: Wed, 15 Aug 2007, 05:50:21 EST