EBV Zta protein induces the expression of interleukin-13, promoting the proliferation of EBV-infected B cells and lymphoblastoid cell lines
Journal
Blood
Journal Volume
114
Journal Issue
1
Pages
109-118
Date Issued
2009
Author(s)
Abstract
Epstein-Barr virus (EBV) infection can modify the cytokine expression profiles of host cells and determine the fate of those cells. Of note, expression of interleukin-13 (IL-13) may be detected in EBV-associated Hodgkin lymphoma and the natural killer (NK) cells of chronic active EBV-infected patients, but its biologic role and regulatory mechanisms are not understood. Using cytokine antibody arrays, we found that IL-13 production is induced in B cells early during EBV infection. Furthermore, the EBV lytic protein, Zta (also known as the BZLF-1 product), which is a transcriptional activator, was found to induce IL-13 expression following transfection. Mechanistically, induction of IL-13 expression by Zta is mediated directly through its binding to the IL-13 promoter, via a consensus AP-1 binding site. Blockade of IL-13 by antibody neutralization showed that IL-13 is required at an early stage of EBV-induced proliferation and for long-term maintenance of the growth of EBV immortalized lymphoblastoid cell lines (LCLs). Thus, Zta-induced IL-13 production facilitates B-cell proliferation and may contribute to the pathogenesis of EBV-associated lymphoproliferative disorders, such as posttransplantation lymphoproliferative disease (PTLD) and Hodgkin lymphoma. ? 2009 by The American Society of Hematology.
SDGs
Other Subjects
immediate early protein BZLF1; interleukin 13; interleukin 13 antibody; transcription factor AP 1; BZLF1 protein, Herpesvirus 4, Human; interleukin 13; primer DNA; transactivator protein; virus DNA; article; B lymphocyte; binding site; cell fate; cell immortalization; controlled study; cytokine production; embryo; Epstein Barr virus; genetic transfection; Hodgkin disease; human; human cell; lymphoblastoid cell; lymphocyte culture; lymphocyte proliferation; lymphoproliferative disease; nonhuman; posttransplantation lymphoproliferative disease; priority journal; promoter region; protein binding; virus etiology; virus infection; biosynthesis; cell line; cell proliferation; DNA methylation; gene expression; genetics; Hodgkin disease; immunology; lymphocyte; lymphoproliferative disease; nucleotide sequence; pathogenicity; pathology; physiology; transcription initiation; tumor cell line; virology; virus infection; B-Lymphocytes; Base Sequence; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; DNA Methylation; DNA Primers; DNA, Viral; Epstein-Barr Virus Infections; Gene Expression; Herpesvirus 4, Human; Hodgkin Disease; Humans; Interleukin-13; Lymphocytes; Lymphoproliferative Disorders; Promoter Regions, Genetic; Trans-Activators; Transcriptional Activation
Publisher
American Society of Hematology
Type
journal article