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.
DSC2 as the Missing Receptor: Through CRISPR and siRNA screening in HEK293 cells, researchers identified DSC2 as essential for EBV epithelial cell entry.
Cross-Species Infection Enabled: Expression of human DSC2 in hamster cells (CHO-K1) rendered them susceptible to EBV infection.
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
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.)