7SFU

CryoEM structure of Venezuelan Equine Encephalitis virus (VEEV) TC-83 strain VLP

Summary for 7SFU

• Entry DOI: 10.2210/pdb7sfu/pdb
• EMDB information: 25102 25103
• Descriptor: Spike glycoprotein E1, Spike glycoprotein E2, Capsid protein, ... (4 entities in total)
• Functional Keywords: vlp, veev, viral protein, virus
• Biological source: Venezuelan equine encephalitis virus (strain TC-83) (VEEV); More
• Total number of polymer chains: 12
• Total formula weight: 455701.10

Authors

Binshtein, E.,Crowe, J.E. (deposition date: 2021-10-04, release date: 2022-03-16, Last modification date: 2024-10-23)

Primary citation

Kafai, N.M.,Williamson, L.E.,Binshtein, E.,Sukupolvi-Petty, S.,Gardner, C.L.,Liu, J.,Mackin, S.,Kim, A.S.,Kose, N.,Carnahan, R.H.,Jung, A.,Droit, L.,Reed, D.S.,Handley, S.A.,Klimstra, W.B.,Crowe, J.E.,Diamond, M.S.
Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge.
J.Exp.Med., 219:-, 2022

PubMed Abstract: Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development.

PubMed: 35297953
DOI: 10.1084/jem.20212532

Experimental method

ELECTRON MICROSCOPY (4.2 Å)