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A New Humanized Mouse Model of Epstein‐Barr Virus Infection That Reproduces Persistent Infection, Lymphoproliferative Disorder, and Cell‐Mediated and Humoral Immune Responses
Abstract
The functional human immune system, including T, B, and natural killer lymphocytes, is reconstituted in NOD/Shi-scid/IL-2Rγnull (NOG) mice that receive hematopoietic stem cell transplants. Here, we show that these humanized mice can recapitulate key aspects of Epstein-Barr virus (EBV) infection in humans. Inoculation with ∼1 × 103 TD50 (50% transforming dose) of EBV caused B cell lymphoproliferative disorder, with histopathological findings and latent EBV gene expression remarkably similar to that in immunocompromised patients. Inoculation with a low dose of virus (≤1 × 101 TD50), in contrast, resulted in apparently asymptomatic persistent infection. Levels of activated CD8+ T cells increased dramatically in the peripheral blood of infected mice, and enzyme-linked immunospot assay and flow cytometry demonstrated an EBV-specific T cell response. Immunoglobulin M antibody specific to the EBV-encoded protein BFRF3 was detected in serum from infected mice. The NOG mouse is the most comprehensive small-animal model of EBV infection described to date and should facilitate studies of the pathogenesis, prevention, and treatment of EBV infection.
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Self-citationWoon, H. G., Braun, A., Li, J., Smith, C., Edwards, J., Sierro, F., Feng, C. G., Khanna, R., Elliot, M., Bell, A., et al. (2016) · PLOS Pathogens · doi:10.1371/journal.ppat.1005799 · Cited by 97
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Metadata
- Authors
- Yajima, M., Imadome, K., Nakagawa, A., Watanabe, S., Terashima, K., Nakamura, H., Ito, M., Shimizu, N., Honda, M., Yamamoto, N., & Fujiwara, S.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09
- Volume
- 198
- Issue
- 5
- Pages
- 673-682
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W1976701849
- Cited by
- 183
- References
- 0
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: A New Humanized Mouse Model of Epstein‐Barr Virus Infection That Reproduces Persistent Infection, Lymphoproliferative Disorder, and Cell‐Mediated and Humoral Immune Responses. https://app.cochat.ai/papers/10.1086/590502
- The paper
- Yajima, M., Imadome, K., Nakagawa, A., Watanabe, S., Terashima, K., Nakamura, H., Ito, M., Shimizu, N., Honda, M., Yamamoto, N., & Fujiwara, S. (2008). A New Humanized Mouse Model of Epstein‐Barr Virus Infection That Reproduces Persistent Infection, Lymphoproliferative Disorder, and Cell‐Mediated and Humoral Immune Responses. The Journal of Infectious Diseases. https://doi.org/10.1086/590502
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