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Humanized Mouse Models of Epstein Barr Virus Infection
Saskia Gertrud von Boxberg1, Kristin Gehrmann1, Svenja Luisa Nopper1
1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
Current Protocols
|November 25, 2025
Summary
This study details a humanized mouse model for Epstein-Barr virus (EBV) infection, enabling the study of infectious mononucleosis (IM) and EBV-driven lymphomas. The model allows for analysis of viral loads, immune responses, and potential therapeutic interventions.
Area of Science:
- Immunology
- Virology
- Pathogenesis
Background:
- Epstein-Barr virus (EBV) is a human herpesvirus causing infectious mononucleosis (IM) and implicated in various cancers.
- Studying EBV pathogenesis requires a suitable animal model, as EBV primarily infects human B cells.
- Existing models often necessitate the transfer of human immune components into immunocompromised hosts.
Purpose of the Study:
- To establish and validate a humanized mouse model for studying EBV infection and associated diseases.
- To enable the investigation of EBV's primary infection, latency, and oncogenic potential in vivo.
- To provide a platform for evaluating immune responses and therapeutic strategies against EBV.
Main Methods:
- Neonatal transfer of CD34+ hematopoietic progenitor cells into immune-compromised NOD-scid γc-/- (NSG) mice to reconstitute the human immune system.
- Infection of humanized mice with a recombinant EBV strain (B95-8) via intraperitoneal or intranasal routes.
- Monitoring of viral loads, B-cell lymphoproliferation, T-cell responses (CD8+ T-cell lymphocytosis), and lymphoma development using techniques like immunohistochemistry and spectral flow cytometry.
Main Results:
- Successful reconstitution of human immune system components, including B cells, in NSG mice.
- EBV infection in humanized mice mimicked symptomatic primary infection (infectious mononucleosis) with high viral loads.
- Development of clonal EBV-induced B-cell lymphoproliferations resembling large B-cell lymphomas with EBV latency III program.
- Characterization of CD8+ T-cell expansion and viral load dynamics post-infection.
Conclusions:
- The developed humanized mouse model provides a robust platform for studying EBV pathogenesis, including IM and EBV-associated lymphomas.
- This model facilitates research into EBV-mediated immune responses and the evaluation of potential vaccines and therapies.
- The model has been instrumental in exploring EBV mutant infections, co-infections (HIV, KSHV), and antibody-mediated protection.
