title: Epstein-Barr virus LMP2A increases IL-10 production in mitogen-stimulated primary B-cells and B-cell lymphomas.
abstract: Epstein-Barr virus (EBV) latently infected B-cells are the precursors of EBV-associated malignancies. EBV-infection induces the production of pro-survival and anti-inflammatory cytokines that may be important in the transition between latency and malignancy. One EBV protein, LMP2A, can be detected in both latently infected resting B-cells and in EBV-associated malignancies. Therefore, we tested the ability of LMP2A to influence cytokine production using both LMP2A-Tg primary B-cells and LMP2A-expressing B-cell lines. Our data demonstrate that LMP2A does not globally alter B-cell-produced cytokine levels, but specifically targets IL-10. Additional studies using ELISA and real-time-RT-PCR confirm that LMP2A utilizes PI3-kinase to increase IL-10 levels. Finally, the data demonstrate that LMP2A-expressing B-cell lines are more dependent on IL-10 for survival in comparison to LMP2A-negative B-cell lines. These data identify a novel function of LMP2A in the alteration of a cytokine that is important for both tumour survival and anti-tumour responses.
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Incrocci
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: McCormack
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Swanson-Mungerson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D008934:Mitogens / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C556062:IL10 protein, mouse; D008934:Mitogens; D014763:Viral Matrix Proteins; D016753:Interleukin-10; D058539:Phosphatidylinositol 3-Kinase