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Updated: Jul 8, 2026
Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
A new animal model for primary and persistent Epstein-Barr virus infection: human EBV-infected rabbit characteristics
Kazuaki Takashima1, Makoto Ohashi, Yukisato Kitamura
1Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.
Abstract:
Most adults have persistent Epstein-Barr virus (EBV)-infection. Adolescents and young adults with primary EBV-infection frequently develop infectious mononucleosis. Latent EBV-infection is associated with various diseases, neoplasms, and hematological disorders. In vivo animal models of human EBV infection, such as non-human primates, have had limited success. A new rabbit model for primary human EBV-infection is described in this study. Seven male rabbits inoculated intravenously with EBV were sequentially imaged by ultrasonography and computed tomography, and examined for anti-EBV-VCA titer and EBV-DNA levels in blood. Six rabbits demonstrated transient splenomegaly, increased anti-EBV-VCA titers and/or EBV-DNA in blood. Transient infiltration of some EBER1-positive lymphocytes was observed in biopsied liver tissues. After splenomegaly, two rabbits tested continuously negative, two alternatively positive and negative, and one consistently positive EBV detection in blood for 470 days. One tested negative for both EBV DNA and splenomegaly. On the 14th day, mild to moderate numbers of EBER1-positive lymphocytes expressing LMP1, EBNA2, or ZEBRA infiltrated mainly in enlarged white pulps of two splenectomized materials. These cells included both B and T cells. EBV clonality analysis revealed an oligoclonal pattern. These indicate that EBV-inoculated rabbits exhibiting heterogenous host reactions are a good model for primary and persistent human EBV infection.
Insights
A new rabbit model effectively mimics primary Epstein-Barr virus (EBV) infection in humans. This model shows EBV-induced splenomegaly and detectable viral DNA, offering a valuable tool for studying EBV pathogenesis.
Area of Science:
- Virology
- Immunology
- Animal Models
Background:
- Epstein-Barr virus (EBV) establishes persistent infections in most adults.
- Primary EBV infection in adolescents can cause infectious mononucleosis.
- Latent EBV infection is linked to various diseases and cancers.
Purpose of the Study:
- To develop and characterize a novel rabbit model for primary human EBV infection.
- To evaluate the host response to EBV inoculation in rabbits.
Main Methods:
- Seven male rabbits were intravenously inoculated with EBV.
- Sequential ultrasonography and computed tomography were used for imaging.
- Anti-EBV-VCA titers and EBV-DNA levels in blood were monitored.
- Liver tissues were biopsied and examined for viral markers and immune cell infiltration.
Main Results:
- Six of seven rabbits showed transient splenomegaly and/or detectable EBV-DNA or anti-EBV-VCA titers.
- Transient infiltration of EBER1-positive lymphocytes was observed in liver tissues.
- EBV detection in blood varied among rabbits, with some showing persistent positivity for up to 470 days.
- Infiltrating lymphocytes in spleen tissues included both B and T cells expressing EBV latent proteins.
Conclusions:
- EBV-inoculated rabbits exhibit heterogeneous host responses, mimicking human EBV infection.
- This rabbit model is suitable for studying primary and persistent human EBV infection.
- The model allows for investigation of EBV-associated immune responses and pathogenesis.
