Structure of the Epstein-Barr virus major envelope glycoprotein.

in Nature structural & molecular biology by Gerda Szakonyi, Michael G Klein, Jonathan P Hannan, Kendra A Young, Runlin Z Ma, Rengasamy Asokan, V Michael Holers, Xiaojiang S Chen

TLDR

  • The study is about understanding how a virus called Epstein-Barr virus (EBV) infects cells. The virus has a protein called gp350 that binds to a cell surface receptor called CR2. The study determined the structure of gp350 and found that the part of the protein that binds to CR2 is not covered in sugar molecules, but rather a 'naked' surface. The study also found that glycosylation, which is the addition of sugar molecules to the protein, is not important for binding to CR2. The study provides information that can help researchers develop drugs and vaccines to prevent EBV infection.

Abstract

Epstein-Barr virus (EBV) infection of B cells is associated with lymphoma and other human cancers. EBV infection is initiated by the binding of the viral envelope glycoprotein (gp350) to the cell surface receptor CR2. We determined the X-ray structure of the highly glycosylated gp350 and defined the CR2 binding site on gp350. Polyglycans shield all but one surface of the gp350 polypeptide, and we demonstrate that this glycan-free surface is the receptor-binding site. Deglycosylated gp350 bound CR2 similarly to the glycosylated form, suggesting that glycosylation is not important for receptor binding. Structure-guided mutagenesis of the glycan-free surface disrupted receptor binding as well as binding by a gp350 monoclonal antibody, a known inhibitor of virus-receptor interactions. These results provide structural information for developing drugs and vaccines to prevent infection by EBV and related viruses.

Overview

  • The study focuses on the association between Epstein-Barr virus (EBV) infection of B cells and lymphoma and other human cancers. The hypothesis being tested is the role of the viral envelope glycoprotein (gp350) in the binding of EBV to the cell surface receptor CR2. The methodology used for the experiment includes determining the X-ray structure of the highly glycosylated gp350 and defining the CR2 binding site on gp350. The primary objective of the study is to provide structural information for developing drugs and vaccines to prevent infection by EBV and related viruses.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions, specifically the binding of glycosylated and deglycosylated gp350 to CR2. The results show that glycosylation is not important for receptor binding, as both glycosylated and deglycosylated gp350 bound CR2 similarly. Structure-guided mutagenesis of the glycan-free surface disrupted receptor binding as well as binding by a gp350 monoclonal antibody, a known inhibitor of virus-receptor interactions. These findings provide insights into the mechanism of EBV infection and can inform the development of drugs and vaccines targeting the glycan-free surface of gp350.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they provide structural information for developing drugs and vaccines to prevent infection by EBV and related viruses. The limitations of the study include the use of in vitro experiments and the need for further validation in vivo. Future research directions could include the development of small molecule inhibitors targeting the glycan-free surface of gp350 or the use of CRISPR-Cas9 technology to modify the gp350 gene and study its effects on EBV infection. Additionally, the study highlights the importance of understanding the molecular mechanisms of virus-receptor interactions in the development of effective drugs and vaccines.
Read Full Article