title: Epstein-Barr virus modulates host cell microRNA-194 to promote IL-10 production and B lymphoma cell survival.
abstract: 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.
authors.affiliation: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA.|Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA.
authors.forename: A
authors.initials: A
authors.lastname: Harris-Arnold
authors.affiliation: Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA.
authors.forename: C P
authors.initials: CP
authors.lastname: Arnold
authors.affiliation: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA.|Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA.
authors.forename: S
authors.initials: S
authors.lastname: Schaffert
authors.affiliation: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA.|Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA.
authors.forename: O
authors.initials: O
authors.lastname: Hatton
authors.affiliation: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA.|Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA.
authors.forename: S M
authors.initials: SM
authors.lastname: Krams
authors.affiliation: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA.
authors.forename: C O
authors.initials: CO
authors.lastname: Esquivel
authors.affiliation: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA.|Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA.
authors.forename: O M
authors.initials: OM
authors.lastname: Martinez
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D002470:Cell Survival; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000473:pathology / Q000821:virology*; D035683:MicroRNAs / Q000378:metabolism; D016377:Organ Transplantation / Q000009:adverse effects; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D014407:Tumor Cells, Cultured
chemical_list: C508609:IL10 protein, human; D035683:MicroRNAs; D016753:Interleukin-10
keywords: Cellular biology; infectious disease; molecular biology