Neutralizing human monoclonal antibodies to poliovirus map to the receptor binding site

TL;DR

Scientists identified human antibodies that neutralize all three types of poliovirus by mimicking the virus's receptor binding, which could help in developing antiviral treatments.

Contribution

The study provides high-resolution structures of poliovirus-antibody complexes, revealing how antibodies mimic receptor binding to neutralize the virus.

Findings

Human monoclonal antibodies bind to the poliovirus receptor binding site, neutralizing all three serotypes.

Structural analysis shows antibody binding overlaps with the poliovirus receptor's interaction site on the viral capsid.

Cross-neutralizing antibodies bind deep in the capsid canyon, suggesting a mechanism for broad antiviral activity.

Abstract

Poliovirus remains a serious threat to human health. Complete eradication of wild-type poliovirus has not yet succeeded, making the development of successful antivirals critical. Microneutralization assays against all three poliovirus serotypes identified a panel of human monoclonal IgGs, which are either serotype-specific or cross-neutralizing. Here, through cryoEM single particle analysis, we solved high resolution structures of four distinct poliovirus-FAb complexes. These antibodies bind to capsids at the circular depression (canyon) surrounding the icosahedral five-fold symmetry axis, which is also the binding site of the poliovirus receptor (PVR). Analysis of these structures confirms overlap of FAb contacts on the viral capsid with those of PVR. For three of the FAbs, the capsid residues are identified that dictate serotype-specific recognition. Contacts for the cross-neutralizing mAb 10D2 are located deep in the capsid canyon. These structural analyses indicate that antibody competition with the receptor likely leads to neutralization of virus particles and inhibition of poliovirus entry into host cells. Thus, the human IgGs studied here may facilitate development of therapeutics for the ongoing efforts in global eradication of poliovirus.

The authors detail human antibodies that neutralize all three serotypes of poliovirus and mimic poliovirus receptor binding, accelerating antiviral development to further efforts to eradicate poliovirus.

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