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Epstein–Barr Virus Modulates Host Cell MicroRNA‐194 to Promote IL‐10 Production and B Lymphoma Cell Survival
Author(s) -
HarrisArnold A.,
Arnold C. P.,
Schaffert S.,
Hatton O.,
Krams S. M.,
Esquivel C. O.,
Martinez O. M.
Publication year - 2015
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13375
Subject(s) - medicine , donation , intensive care medicine , economics , economic growth
Epstein–Barr virus (EBV) is a γ‐herpesvirus that is linked to the development of posttransplant lymphoproliferative disorder (PTLD) in solid organ recipients. We previously demonstrated that EBV + B cell lymphoma cell lines isolated from patients with PTLD produce human IL‐10 as an autocrine growth factor. However, little is known regarding IL‐10 regulation in B cells. Here we show that EBV infection markedly alters the expression of host B cell microRNA, a class of small noncoding RNA that is an important regulator of transcriptional and posttranscriptional gene expression. Gene arrays reveal unique microRNA profiles in EBV + B cell lymphoma lines from patients with PTLD, compared to normal B cells or in vitro generated EBV + lymphoblastoid cell lines. We show that microRNA‐194 expression is uniquely suppressed in EBV + B cell lines from PTLD patients and that the 3'untranslated region of IL‐10 is targeted by microRNA‐194. Overexpression of microRNA‐194 attenuates IL‐10 production and increases apoptosis of EBV + B cell lymphoma lines. Together, these data indicate that EBV co‐opts the host B cell microRNA network and specifically suppresses microRNA‐194 to override control of IL‐10 expression. Thus, modulation of microRNA‐194 may constitute a novel approach to inhibiting proliferation of EBV + B cell lymphomas in PTLD.