Viral neutralization by antibody-imposed physical disruption

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Adaptive immunity relies on neutralizing antibodies (nAbs) to combat pathogens.
• The precise mechanisms of viral neutralization are diverse and still under investigation.

Purpose of the Study:

• To investigate a novel viral neutralization mechanism involving physical disruption by nAbs.
• To elucidate the mechanism of a potent nAb (8C11) against hepatitis E virus (HEV).

Main Methods:

• Utilized cryo-electron microscopy to reconstruct HEV viruslike particle (VLP) dissociation intermediates.
• Performed ultracentrifugation to analyze the integrity of HEV virions after antibody treatment.

Main Results:

• The nAb 8C11 binds to HEV VLPs, causing physical collision and dissociation into homodimers within 2 hours.
• Cryo-EM revealed structural disruption, including smeared spikes and loss of icosahedral symmetry, while the capsid core remained intact.
• Antibody treatment resulted in fewer intact HEV virions and exposed viral genomes.

Conclusions:

• Proposed a new neutralization strategy based on inducing physical collision with nAbs against pathogen spike proteins.
• This collision-inducing nAb approach could lead to innovative vaccine development and antimicrobial antibody design.