Assembly and architecture of the EBV B cell entry triggering complex.

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Epstein-Barr virus (EBV), a gammaherpesvirus, infects human epithelial and B cells.
• EBV entry into B cells involves a complex of glycoproteins gH, gL, and gp42, interacting with host HLA class II receptors.

Purpose of the Study:

• To investigate the assembly and function of the EBV B cell entry complex.
• To elucidate the mechanistic role of the gHgL complex in viral entry and membrane fusion.

Main Methods:

• Negative-stain electron microscopy to determine the structure of the reconstituted EBV B cell entry complex.
• Biochemical analysis of gHgL interactions with gp42 and functional assays for membrane fusion.

Main Results:

• The structure revealed an intermediate state in EBV entry, showing the complex positioned to bring viral and host membranes together.
• The gHgL complex interacts with a hydrophobic pocket on gp42, defining the overall architecture and activating membrane fusion.
• The study proposes a model for EBV B cell fusion initiation mediated by the triggering complex.

Conclusions:

• The EBV gHgL-gp42-HLA class II complex plays a critical role in initiating membrane fusion for B cell entry.
• Understanding this complex provides insights into gammaherpesvirus entry mechanisms and potential therapeutic targets.