Viral neutralization by antibody-imposed physical disruption

Abstract

In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans

“…The genome of HEV contains three open-reading frames (ORFs), of which ORF2 encodes a major viral capsid protein of 660 amino acids (aa) associated with virion assembly, host interaction, and immunogenicity 15 . The E2s domain (aa 459–606) of the capsid protein forms a homodimer on the virus surface, mediates virus–host interactions, and presents a major target for immune recognition 17 – 19 . All E2s domains adopt a similar structure 20 , 21 , with an aa-level sequence identity of 83–97% across different genotypes.…”

Purple Potato Extract Promotes Intestinal Epithelial Differentiation and Barrier Function by Activating AMP‐Activated Protein Kinase

“…[12] Furthermore, polyphenol extracts are known to activate adenosine monophosphate-activated protein kinase (AMPK), [9] an energy sensor that regulates tight junctions and epithelial permeability. [13] Purple potato is a source of polyphenols. [14] Purple potato extract (PPE) has health beneficial effects, such as antioxidative, [15] antitumor, [16] and antimicrobial [17] activity.…”

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants

“…Regarding to viral neutralization mechanism, the established SARS-CoV-2 cross-neutralizing antibody CR3022 provides neutralization through antibody-induced spike disruption 24 . Similarly, we previously showed that the 8C11 antibody can neutralize native Hepatitis E virus (HEV) by antibody-imposed physical disruption 52 . Indeed, although the 7D6/6D6 site is inaccessible for antibody binding to the trimeric spike, 7D6 and 6D6 could still associate with the S-2P protein with excellent a nities (Fig.…”