In silico epitope prediction and evolutionary analysis reveals capsid mutation patterns for enterovirus B

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Enterovirus B (EVB) is a prevalent viral species causing serious diseases like meningitis and myocarditis.
• Previous studies determined EVB structures and identified some neutralizing antibody epitopes, but potential additional epitopes and their evolutionary role remain unclear.
• Understanding EVB epitope dynamics is crucial for developing effective therapeutics and monitoring epidemics.

Purpose of the Study:

• To systematically predict conformational epitopes of six representative EVB serotypes using bioinformatics.
• To analyze molecular evolution of EVB epitopes and their relationship with receptor binding sites.
• To investigate the role of epitope mutations in EVB evolution and epidemic spread.

Main Methods:

• Bioinformatics-based epitope prediction algorithm applied to six EVB serotypes (E6, E11, E30, CVB1, CVB3, CVB5).
• Conformational epitope mapping and clustering.
• Molecular evolution analysis using VP1 and genome sequences.
• Analysis of mutation distribution relative to epitopes and receptor binding sites.

Main Results:

• Epitopes were clustered in VP1 BC loop, C-terminus, and VP2 EF loop, with VP1 BC and VP2 EF loops potentially mediating receptor binding.
• VP1 C-terminus, VP2 EF loop, and VP1 N-terminus were identified as common mutation hotspots.
• Epitope mutations were found to drive the emergence of evolutionary clades.
• Mutations primarily occurred on or near epitopes, while receptor binding sites remained largely conserved.

Conclusions:

• EVB promotes epidemics by altering its immune-evading epitopes, while preserving essential receptor binding sites.
• Epitope mutations are a key driver of EVB molecular evolution and clade emergence.
• This bioinformatics study provides valuable data for EVB epidemic surveillance and the development of targeted therapeutic antibodies.