Structural basis for complement receptor engagement and virus neutralization through Epstein-Barr virus gp350

Area of Science:

• Structural biology
• Virology
• Immunology

Background:

• Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to human cancers.
• EBV infects B cells via its glycoprotein 350 (gp350) binding to complement receptor 2 (CR2).
• Lack of atomic-level understanding of the virus-host interface hinders EBV vaccine and therapeutic development.

Purpose of the Study:

• To determine the atomic-level structure of the EBV gp350-CR2 complex.
• To investigate the structural basis of neutralizing antibody interactions with gp350.
• To provide insights for developing EBV vaccines and therapeutics.

Main Methods:

• X-ray crystallography was used to determine the structures of gp350 in complex with CR2 and neutralizing antibodies.
• Structural analysis focused on identifying key residues and interaction interfaces.

Main Results:

• The 1.7 Å structure of gp350 complexed with CR2 was determined.
• gp350 utilizes specific arginine residues for CR2 binding, mimicking its interaction with complement C3d.
• Structures of gp350 with three neutralizing antibodies revealed they target the CR2-binding site using similar arginine residues.

Conclusions:

• The study elucidates the molecular mimicry between EBV gp350-CR2 interaction and the gp350-antibody interaction.
• Findings offer a structural basis for understanding EBV entry and antibody neutralization.
• The identified structural features provide critical insights for designing effective EBV vaccines and antiviral therapies.