Human herpesvirus 6B glycoprotein B postfusion structure, vulnerability mapping, and receptor recognition

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Human herpesvirus 6B (HHV-6B) poses a significant threat to immunocompromised individuals.
• Current therapeutic options and vaccines for HHV-6B are limited.
• Glycoprotein B (gB) is crucial for viral entry and a key target for antibody and vaccine development.

Purpose of the Study:

• To determine the cryo-EM structure of the HHV-6B gB ectodomain.
• To identify unique structural features and conserved residues across herpesviruses.
• To explore potential vulnerable sites on HHV-6B gB for therapeutic targeting.

Main Methods:

• Cryo-electron microscopy (cryo-EM) at 2.8 Å resolution.
• Comparative structural analysis with related herpesvirus gB proteins.
• Cross-binding assays using neutralizing antibodies (nAbs).

Main Results:

• The postfusion conformation of the HHV-6B gB ectodomain was resolved.
• Unique N-terminal features and the furin site were identified.
• Conserved residues across herpesviruses were mapped, and minimal cross-epitope recognition by heterologous nAbs was observed.
• Several potential vulnerable sites on HHV-6B gB were identified.

Conclusions:

• The determined structure provides critical insights into HHV-6B infection mechanisms.
• Understanding HHV-6B gB structure facilitates the development of targeted antiviral therapies and vaccines.
• The identified vulnerable sites offer promising avenues for future drug and vaccine design.