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.
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http://dx.doi.org/10.1186/s12985-018-0970-2 | DOI Listing |
J Gen Virol
January 2025
Biochemistry Program, The University of the South, Sewanee, TN, USA.
The murine hepatitis virus (MHV) is an important model system for studying coronavirus (CoV) molecular and cell biology. Despite this, few reagents for MHV are available through repositories such as ATCC or Addgene, potentially limiting the widespread adoption of MHV as a tractable model system. To overcome some challenges inherent in the existing MHV reverse genetics systems, we developed a plasmid-launched transformation-associated recombination (TAR) cloning-based system to assemble the MHV (strain A59; MHV-A59) genome.
View Article and Find Full Text PDFJ Extracell Vesicles
January 2025
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China.
Japanese encephalitis virus (JEV) is a neurotropic zoonotic pathogen that poses a serious threat to public health. Currently, there is no specific therapeutic agent available for JEV infection, primarily due to the complexity of its infection mechanism and pathogenesis. Extracellular vesicles (EVs) have been known to play an important role in viral infection, but their specific functions in JEV infection remain unknown.
View Article and Find Full Text PDFNature
January 2025
Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China.
Mimicking the superstructures and properties of spherical biological encapsulants such as viral capsids and ferritin offers viable pathways to understand their chiral assemblies and functional roles in living systems. However, stereospecific assembly of artificial polyhedra with mechanical properties and guest-binding attributes akin to biological encapsulants remains a formidable challenge. Here we report the stereospecific assembly of dynamic supramolecular snub cubes from 12 helical macrocycles, which are held together by 144 weak C-H hydrogen bonds.
View Article and Find Full Text PDFFront Microbiol
December 2024
Infection Biology Laboratory, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONI-CET-UNT, Tucumán, Argentina.
Introduction: The development of a hepatitis E virus (HEV) vaccine is critical, with ORF2 capsid protein as the main target. We previously demonstrated that oral coadministration of recombinant ORF2 with immunomodulatory bacterium-like-particles (IBLP) induces a specific immune response in mice, particularly using IBLP derived from IBL027 (IBLP027), which was effective in eliciting a local humoral response. IBLP are non-live bacteria with adjuvant and carrier properties, serving as a platform for exposing proteins or antigens fused to LysM (lysine motif) domains, protein modules that bind to cell wall polysaccharides like peptidoglycan.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China.
Adeno-associated virus (AAV) vectors are a leading platform for gene therapy. Recently, AAV-mediated gene therapy in the inner ear has progressed from laboratory use to clinical trials, but the lower transduction rates in outer hair cells (OHCs) in the organ of Corti and in vestibular hair cells in adult mice still pose a challenge. OHCs are particularly vulnerable to inner ear insults.
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