6lm3 | pdb_00006lm3
Neutralization mechanism of a monoclonal antibody targeting a porcine circovirus type 2 Cap protein conformational epitope
Structural highlights
Publication Abstract from PubMedPorcine circovirus type 2 (PCV2) is an important pathogen in swine herds, and its infection in pigs has caused severe economic losses to the pig industry worldwide. The capsid protein of PCV2 is the only structural protein that is associated with PCV2 infection and immunity. Here, we report a neutralizing monoclonal antibody (mAb), 3A5, which binds to intact PCV2 virions of PCV2a, PCV2b and PCV2d genotypes. The mAb 3A5 neutralized PCV2 by blocking viral attachment to PK15 cells. To further explore the neutralization mechanism, we resolved the structure of the PCV2 virion in complex with mAb 3A5 Fab fragments by using cryo-electron microscopy (cryo-EM) single particle analysis. The binding sites were located at the topmost edges around fivefold icosahedral symmetry axes, with each footprint covering amino acids from two adjacent capsid proteins. Most of the epitope residues (15/18) are conserved among 2,273 PCV2 strains. Mutations of some amino acids within the epitope had a significant effect on the neutralizing activity of mAb 3A5. This study reveals the molecular and structural basis of this PCV2-neutralizing antibody and provides new and important information for vaccine design and therapeutic antibody development against PCV2 infections.IMPORTANCEPorcine circovirus type 2 (PCV2) is associated with several clinical manifestations collectively known as porcine circovirus-associated diseases (PCVADs). Neutralizing antibodies play a crucial role in the prevention of PCVADs. We have previously demonstrated that a monoclonal antibody (mAb), 3A5, neutralizes the PCV2a, PCV2b and PCV2d genotypes with different degrees of efficiencies, but the underlying mechanism remains elusive. Here, we report the neutralization mechanism of this mAb and the structure of the PCV2 virion in complex with the mAb 3A5 Fabs, showing a binding mode in which one Fab interacted with more than two loops from two adjacent capsid proteins. This binding mode has not been observed before for PCV2 neutralizing antibodies. Our work provides new and important information for vaccine design and therapeutic antibody development against PCV2 infections. Neutralization Mechanism of a Monoclonal Antibody Targeting a Porcine Circovirus Type 2 Cap Protein Conformational Epitope.,Huang L, Sun Z, Xia D, Wei Y, Sun E, Liu C, Zhu H, Bian H, Wu H, Feng L, Wang J, Liu C J Virol. 2020 Feb 19. pii: JVI.01836-19. doi: 10.1128/JVI.01836-19. PMID:32075932[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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