Structural basis of Epstein-Barr virus gp350 receptor recognition and neutralization

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Epstein-Barr virus (EBV) is linked to lymphoid malignancies and autoimmune disorders.
• EBV utilizes its glycoprotein gp350 to bind complement receptor 2 (CR2) on B cells for viral attachment.
• Direct structural evidence for the gp350-CR2 interaction has been elusive.

Purpose of the Study:

• To determine the structure of the gp350-CR2 complex.
• To elucidate the molecular interactions between gp350 and CR2.
• To investigate the role of N-glycosylation on gp350.

Main Methods:

• X-ray crystallography to resolve the gp350-CR2 complex structure.
• Site-specific N-glycosylation mapping of gp350.
• Construction and testing of a CR2-Fc antibody analog.

Main Results:

• The gp350-CR2 complex structure revealed an electrostatically driven, glycan-free binding interface.
• Key residues in CR2 influence EBV host selectivity via gp350 interaction.
• A CR2-Fc antibody analog effectively neutralized EBV infection in B cells.

Conclusions:

• Structural insights clarify EBV attachment mechanism and host tropism.
• The identified binding site on gp350 is a target for antiviral strategies.
• A CR2-Fc antibody analog shows promise as a therapeutic agent against EBV.