Sun Yat-sen University Team Discovers Novel EBV Infection Receptor - A Breakthrough for Animal Model Development

                     Sun Yat-sen University Team Discovers Novel EBV Infection Receptor - A Breakthrough for Animal Model Development

Abstract

A research team from Sun Yat-sen University Cancer Center has made a groundbreaking discovery, identifying desmocollin-2 (DSC2) as a novel receptor enabling Epstein-Barr virus (EBV) infection of non-human cells. Published in Nature Microbiology, this study provides crucial insights for developing EBV-infected animal models, particularly for nasopharyngeal carcinoma research. The team demonstrated that DSC2 interacts with EBV glycoProteins gH/gL and works synergistically with EphA2 to mediate viral entry into epithelial cells. This discovery overcomes a major hurdle in EBV research by enabling the creation of susceptible rodent cell lines for future animal model development.

Source

Nature Microbiology, Sun Yat-sen University Cancer Center

Content

In a significant advancement for virology research, Prof. Zeng Musheng's team at Sun Yat-sen University Cancer Center has identified desmocollin-2 (DSC2) as a critical receptor facilitating EBV infection of non-human epithelial cells. Published on July 25 in Nature Microbiology, this discovery provides the foundation for developing much-needed animal models of EBV infection and associated malignancies.

Research Background

EBV, a gammaherpesvirus, infects over 90% of adults worldwide and is associated with various cancers and autoimmune diseases. While human B cells and epithelial cells are natural hosts, EBV cannot infect non-human cells, severely limiting research options. Previous work by Prof. Zeng's team identified several EBV receptors (NMHC-IIA, NRP1, EphA2) and the universal receptor CD9AP, but the species barrier remained unexplained.

Key Findings

1. DSC2 as the Missing Receptor: Through CRISPR and siRNA screening in HEK293 cells, researchers identified DSC2 as essential for EBV epithelial cell entry.

2. Cross-Species Infection Enabled: Expression of human DSC2 in hamster cells (CHO-K1) rendered them susceptible to EBV infection.

3. Molecular Mechanism:

• DSC2's extracellular domain (preEC-EC2) directly binds EBV gH/gL glycoProteins

• AlphaFold3 modeling predicted critical interaction sites confirmed by mutagenesis

• DSC2 cooperates with EphA2 to complete viral entry

Research Impact

This study:

• Solves the decades-long mystery of EBV's species specificity

• Establishes EBV-susceptible rodent cell lines (CHO-DSC2)

• Provides targets for blocking EBV infection

• Enables development of animal models for:

• Nasopharyngeal carcinoma

• EBV-associated gastric cancer

• Lymphomas

The team's creation of DSC2-expressing rodent cell lines represents a crucial step toward generating the first authentic EBV epithelial infection animal models, which will accelerate research into EBV-associated diseases and therapeutic development.

This work was supported by the National Key R&D Program and National Natural Science Foundation of China.

(For detailed experimental methods and data, please refer to the original publication in Nature Microbiology.)