+Open data
-Basic information
Entry | Database: PDB / ID: 9fjc | |||||||||||||||
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Title | Compact CVB1-VLP (Tween80) | |||||||||||||||
Components |
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Keywords | VIRUS LIKE PARTICLE / coxsackievirus B1 / vaccine / Tween80 | |||||||||||||||
Function / homology | Function and homology information symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / channel activity / endocytosis involved in viral entry into host cell / monoatomic ion transmembrane transport ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / channel activity / endocytosis involved in viral entry into host cell / monoatomic ion transmembrane transport / nucleoside-triphosphate phosphatase / DNA replication / RNA helicase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||||||||
Biological species | Coxsackievirus B1 | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.15 Å | |||||||||||||||
Authors | Plavec, Z. / Butcher, S.J. | |||||||||||||||
Funding support | Finland, 4items
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Citation | Journal: Res Sq / Year: 2024 Title: Comparison of structure and immunogenicity of CVB1-VLP and inactivated CVB1 vaccine candidates. Authors: Saana Soppela / Zlatka Plavec / Stina Gröhn / Minne Jartti / Sami Oikarinen / Mira Laajala / Varpu Marjomaki / Sarah J Butcher / Minna M Hankaniemi Abstract: Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we ...Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we investigated the immunogenicity of virus-like particle (VLP) and inactivated whole-virus vaccines for CVB1 when administrated to mice via either subcutaneous or intranasal routes formulated with and without commercial and experimental adjuvants. Here, the potential of utilizing epigallocatechin-3-gallate (EGCG) as a mucosal adjuvant synergistically with its ability to inactivate the virus were investigated. EGCG had promising adjuvant properties for CVB1-VLP when administered via the parenteral route but limited efficacy via intranasal administration. However, intranasal administration of the formalin-inactivated virus induced high CVB1-specific humoral, cellular, and mucosal immune responses. Also, based on CVB1-specific IgG-antibody responses, we conclude that CVB1-VLP can be taken up by immune cells when administrated intranasally and further structural engineering for the VLP may increase the mucosal immunogenicity. The preparations contained mixtures of compact and expanded A particles with 85% expanded in the formalin-inactivated virus, but only 52% in the VLP observed by cryogenic electron microscopy. To correlate the structure to immunogenicity, we solved the structures of the CVB1-VLP and the formalin-inactivated CVB1 virus at resolutions ranging from 2.15 A to 4.1 A for the expanded and compact VLP and virus particles by image reconstruction. These structures can be used in designing mutations increasing the stability and immunogenicity of CVB1-VLP in the future. Overall, our results highlight the potential of using formalin inactivated CVB1 vaccine in mucosal immunization programs and provide important information for future development of VLP-based vaccines against all enteroviruses. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9fjc.cif.gz | 139.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9fjc.ent.gz | 108.1 KB | Display | PDB format |
PDBx/mmJSON format | 9fjc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9fjc_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 9fjc_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 9fjc_validation.xml.gz | 40.2 KB | Display | |
Data in CIF | 9fjc_validation.cif.gz | 58.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fj/9fjc ftp://data.pdbj.org/pub/pdb/validation_reports/fj/9fjc | HTTPS FTP |
-Related structure data
Related structure data | 50497MC 9fjdC 9fjeC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 25415.807 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus B1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P08291 |
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#2: Protein | Mass: 27839.439 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus B1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P08291 |
#3: Protein | Mass: 26328.764 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus B1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P08291 |
#4: Protein/peptide | Mass: 1967.060 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus B1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P08291 |
#5: Chemical | ChemComp-PLM / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Coxsackievirus B1 / Type: VIRUS Details: Coxsackievirus B1 virus-like particle based on CVB1-10796, isolated from Argentina. Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Coxsackievirus B1 |
Details of virus | Empty: YES / Enveloped: NO / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE |
Natural host | Organism: Homo sapiens |
Virus shell | Name: capsid / Diameter: 30 nm |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 295 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2800 nm / Nominal defocus min: 100 nm |
Image recording | Electron dose: 63.368 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 86988 / Symmetry type: POINT |