Mouse model for acute Epstein-Barr virus infection

Tristan Wirtz, Timm Weber, Sven Kracker, Thomas Sommermann, Klaus Rajewsky, Tomoharu Yasuda

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13821-13826
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number48
DOIs
Publication statusPublished - Nov 29 2016

All Science Journal Classification (ASJC) codes

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    Wirtz, T., Weber, T., Kracker, S., Sommermann, T., Rajewsky, K., & Yasuda, T. (2016). Mouse model for acute Epstein-Barr virus infection. Proceedings of the National Academy of Sciences of the United States of America, 113(48), 13821-13826. https://doi.org/10.1073/pnas.1616574113