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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Proc+Natl+Acad+Sci+U+S+A
2016 ; 113
(48
): 13821-13826
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Mouse model for acute Epstein-Barr virus infection
#MMPMID27856754
Wirtz T
; Weber T
; Kracker S
; Sommermann T
; Rajewsky K
; Yasuda T
Proc Natl Acad Sci U S A
2016[Nov]; 113
(48
): 13821-13826
PMID27856754
show ga
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.
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