|Entry||Database: EMDB / ID: EMD-7513|
|Title||Subtomogram average of mature CHIKV virion budded from human cells|
|Biological species||Chikungunya virus|
|Method||subtomogram averaging / cryo EM / Resolution: 34 Å|
|Authors||Galaz-Montoya JG / Jin J / Sherman MB|
|Citation||Journal: Cell Host Microbe / Year: 2018|
Title: Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane.
Authors: Jing Jin / Jesús G Galaz-Montoya / Michael B Sherman / Stella Y Sun / Cynthia S Goldsmith / Eileen T O'Toole / Larry Ackerman / Lars-Anders Carlson / Scott C Weaver / Wah Chiu / Graham Simmons /
Abstract: Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune ...Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune cells to activate antiviral responses. We describe a mechanism by which NAbs inhibit chikungunya virus (CHIKV), the most common alphavirus infecting humans, by preventing virus budding from infected human cells and activating IgG-specific Fcγ receptors. NAbs bind to CHIKV glycoproteins on the infected cell surface and induce glycoprotein coalescence, preventing budding of nascent virions and leaving structurally heterogeneous nucleocapsids arrested in the cytosol. Furthermore, NAbs induce clustering of CHIKV replication spherules at sites of budding blockage. Functionally, these densely packed glycoprotein-NAb complexes on infected cells activate Fcγ receptors, inducing a strong, antibody-dependent, cell-mediated cytotoxicity response from immune effector cells. Our findings describe a triply functional antiviral pathway for NAbs that might be broadly applicable across virus-host systems, suggesting avenues for therapeutic innovation through antibody design.
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_7513.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 7.16 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Chikungunya virus
|Entire||Name: Chikungunya virus / Number of components: 1|
-Component #1: virus, Chikungunya virus
|Virus||Name: Chikungunya virusChikungunya / Class: VIRION / Empty: No / Enveloped: Yes / Isolate: STRAIN|
|Species||Species: Chikungunya virus / Strain: vaccine strain 181/clone 25|
|Source (natural)||Host Species: Homo sapiens (human) / Host species strain: vaccine strain 181/clone 25|
|Specimen||Specimen state: Cell / Method: cryo EM|
|Sample solution||pH: 7|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
|Imaging||Microscope: JEOL 2200FS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 1 e/Å2 / Illumination mode: OTHER|
|Lens||Imaging mode: BRIGHT FIELD / Energy filter: In-column Omega Filter / Energy window: 0-20 eV|
|Specimen Holder||Model: OTHER|
|Camera||Detector: DIRECT ELECTRON DE-20 (5k x 3k)|
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