Bibliographic Details
| Title: |
Mouse model for acute Epstein--Barr virus infection. |
| Authors: |
Wirtz, Tristan, Weber, Timm, Sommermann, Thomas, Rajewsky, Klaus, Tomoharu Yasuda, Kracker, Sven |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America; 11/29/2016, Vol. 113 Issue 48, p13821-13826, 6p |
| Subject Terms: |
EPSTEIN-Barr virus diseases, CELL proliferation, B cells, T cell receptors, LYMPHOPROLIFERATIVE disorders, IMMUNITY |
| 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. EBVinfected 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 LMPexpressing 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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