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Mouse model for acute Epstein-Barr virus infection

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Item Type:Article
Title:Mouse model for acute Epstein-Barr virus infection
Creators Name:Wirtz, T. and Weber, T. and Kracker, S. and Sommermann, T. and Rajewsky, K. and Yasuda, T.
Abstract:Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.
Keywords:Epstein-Barr Virus, LMP1, LMP2A, Familial Hemophagocytic Lymphohistiocytosis, Post-Transplant Lymphoproliferative Disorder, Ainmals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:113
Number:48
Page Range:13821-13826
Date:29 November 2016
Official Publication:https://doi.org/10.1073/pnas.1616574113
PubMed:View item in PubMed

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