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Journal of Clinical Microbiology, October 2007, p. 3167-3174, Vol. 45, No. 10
0095-1137/07/$08.00+0     doi:10.1128/JCM.01143-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differentiation of West Nile and St. Louis Encephalitis Virus Infections by Use of Noninfectious Virus-Like Particles with Reduced Cross-Reactivity{triangledown} ,{dagger}

Jill A. Roberson, Wayne D. Crill, and Gwong-Jen J. Chang*

Arboviral Diseases Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Fort Collins, Colorado 80521

Received 7 June 2007/ Returned for modification 31 July 2007/ Accepted 14 August 2007

Differential diagnosis of St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) infections can be complicated due to the high degree of cross-reactivity observed in most serodiagnostic assays. In an effort to provide a more specific diagnostic test, we developed virus-like particle (VLP) antigens with reduced cross-reactivity for both SLEV and WNV by identifying and mutating envelope protein amino acids within the cross-reactive epitopes of VLP expression plasmids. To determine the serodiagnostic discriminatory ability of the antigens with reduced cross-reactivity, a panel of 134 human serum samples collected predominately from North American patients with SLEV or WNV infections was used to evaluate the performance of these novel antigens in imunoglobulin M antibody-capture enzyme-linked immunosorbent assays. Positive/negative ratios and the resulting diagnostic classifications were compared between the mutant and the wild-type (WT) VLPs. The mutant VLP antigens were more specific, with higher positive predictive values and higher likelihood ratios than the WT VLP antigens. Both the SLEV and WNV mutant VLPs greatly reduced the observed cross-reactivity, significantly increasing the specificity and sensitivity of the assay. The use of these novel VLP antigens with reduced cross-reactivity in these serodiagnostic assays and others should lead to more accurate diagnoses of current infections, thereby reducing the need for time-consuming and cumbersome confirmatory plaque-reduction neutralization tests to differentiate between SLEV and WNV infections in North America.

* Corresponding author. Mailing address: Division of Vector-Borne Infectious Diseases, 3150 Rampart Road, CDC—Foothills Campus, Fort Collins, CO 80521. Phone: (970) 221-6497. Fax: (970) 226-3599. E-mail: gxc7{at}cdc.gov

{triangledown} Published ahead of print on 22 August 2007.

{dagger} Supplemental material for this article may be found at http://jcm.asm.org/.

Journal of Clinical Microbiology, October 2007, p. 3167-3174, Vol. 45, No. 10
0095-1137/07/$08.00+0     doi:10.1128/JCM.01143-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Chiou, S.-S., Crill, W. D., Chen, L.-K., Chang, G.-J. J. (2008). Enzyme-Linked Immunosorbent Assays Using Novel Japanese Encephalitis Virus Antigen Improve the Accuracy of Clinical Diagnosis of Flavivirus Infections. CVI 15: 825-835 [Abstract] [Full Text]  


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