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Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases
Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
* Author to whom correspondence should be addressed.
Received: 1 February 2013; in revised form: 26 February 2013 / Accepted: 5 March 2013 / Published: 14 March 2013
Abstract: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus.
Keywords: Epstein-Barr virus; humanized mouse; lymphoproliferative disease; EBV-associated hemophagocytic lymphohistiocytosis; rheumatoid arthritis; chronic active EBV infection; latent infection; immune responses; xenograft model
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Fujiwara, S.; Matsuda, G.; Imadome, K.-I. Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases. Pathogens 2013, 2, 153-176.
Fujiwara S, Matsuda G, Imadome K-I. Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases. Pathogens. 2013; 2(1):153-176.
Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi. 2013. "Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases." Pathogens 2, no. 1: 153-176.