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Published on: July 9, 2011
Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope
Stefan W Metz1, Ashlie Thomas2, Laura White2
1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, USA. swmetz@med.unc.edu.
Background:
The 4 dengue serotypes (DENV) are mosquito-borne pathogens that are associated with severe hemorrhagic disease. DENV particles have a lipid bilayer envelope that anchors two membrane glycoproteins prM and E. Two E-protein monomers form head-to-tail homodimers and three E-dimers align to form "rafts" that cover the viral surface. Some human antibodies that strongly neutralize DENV bind to quaternary structure epitopes displayed on E protein dimers or higher order structures forming the infectious virus. Expression of prM and E in cell culture leads to the formation of DENV virus-like particles (VLPs) which are smaller than wildtype virus particles and replication defective due to the absence of a viral genome. There is no data available that describes the antigenic landscape on the surface of flavivirus VLPs in comparison to the better studied infectious virion.
Methods:
A large panel of well characterized antibodies that recognize epitope of ranging complexity were used in biochemical analytics to obtain a comparative antigenic surface view of VLPs in respect to virus particles. DENV patient serum depletions were performed the show the potential of VLPs in serological diagnostics.
Results:
VLPs were confirmed to be heterogeneous in size morphology and maturation state. Yet, we show that many highly conformational and quaternary structure-dependent antibody epitopes found on virus particles are efficiently displayed on DENV1-4 VLP surfaces as well. Additionally, DENV VLPs can efficiently be used as antigens to deplete DENV patient sera from serotype specific antibody populations.
Conclusions:
This study aids in further understanding epitopic landscape of DENV VLPs and presents a comparative antigenic surface view of VLPs in respect to virus particles. We propose the use VLPs as a safe and practical alternative to infectious virus as a vaccine and diagnostic antigen.
Insights
Dengue virus-like particles (VLPs) display key antibody epitopes found on infectious dengue virus, making them suitable for diagnostics. VLPs offer a safe alternative to live virus for vaccine and diagnostic antigen development.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Dengue virus (DENV) is a mosquito-borne pathogen causing severe hemorrhagic disease.
- DENV particles feature envelope glycoproteins (prM and E) forming quaternary structure epitopes recognized by neutralizing antibodies.
- DENV virus-like particles (VLPs) are replication-defective, smaller than virions, and their antigenic surface remains uncharacterized compared to infectious DENV.
Purpose of the Study:
- To compare the antigenic surface landscape of DENV VLPs with infectious DENV particles.
- To evaluate the potential of DENV VLPs in serological diagnostics.
Main Methods:
- Biochemical analytics using a panel of well-characterized antibodies against DENV VLPs and virus particles.
- DENV patient serum depletions using VLPs to assess diagnostic potential.
Main Results:
- DENV VLPs, despite heterogeneity, efficiently display conformational and quaternary structure-dependent epitopes found on infectious DENV.
- DENV VLPs effectively depleted serotype-specific antibodies from patient sera, demonstrating diagnostic utility.
Conclusions:
- DENV VLPs present a comparable antigenic surface to infectious DENV, aiding understanding of the epitopic landscape.
- DENV VLPs are proposed as a safe and practical alternative to infectious virus for vaccine and diagnostic applications.
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