A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71

Area of Science:

• Virology
• Structural Biology
• Molecular Mechanisms

Background:

• Enterovirus 71 (EV71) is a significant cause of hand, foot, and mouth disease in children, associated with severe neurological complications and mortality.
• Currently, no effective vaccines or antiviral treatments are available for EV71 infections.

Purpose of the Study:

• To elucidate the high-resolution structures of mature EV71 and its natural empty particles.
• To characterize the atomic details of enterovirus uncoating intermediates.
• To understand the mechanism of EV71 uncoating triggered by receptor binding.

Main Methods:

• High-resolution structural analysis (likely cryo-electron microscopy or X-ray crystallography) of mature EV71 virions and empty particles.
• Comparative structural analysis to identify differences between mature and empty particles.
• Analysis of capsid protein structures, focusing on hydrophobic pockets and the VP1 GH loop.

Main Results:

• Mature EV71 shares structural similarity with other enteroviruses.
• Empty particles exhibit a markedly expanded structure, representing previously uncharacterized uncoating intermediates.
• Collapsed hydrophobic pockets in the expanded particles explain receptor-binding triggered uncoating.
• The VP1 GH loop functions as a sensor for cellular receptor attachment, initiating a generic uncoating mechanism.

Conclusions:

• The study provides a detailed structural model for enterovirus uncoating.
• The findings reveal the mechanism by which receptor binding triggers EV71 uncoating.
• These structural insights open new avenues for developing therapeutic interventions against EV71 and potentially other enteroviruses.