title: [Molecular mechanisms of Epstein-Barr virus-mediated carcinogeneis].
abstract: Epstein-Barr virus (EBV), a ubiquitous human double stranded DNA virus, is associated with a variety of malignancies including Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). These EBV-associated cancers are characterized by the proliferation of monoclonal EBV-infected cells, and viral gene expression in these cells is limited to a subset of latent genes, indicating that EBV latent genes contribute to carcinogenesis. Here I describe the mechanisms of carcinogenesis by EBV, focusing on the function of two EBV latent gens, latent membrane protein 2A (LMP2A) and EBV-encoded small RNA (EBER). LMP2A, which is known to mimic the B cell receptor (BCR) signaling, has been reported to contribute to malignant lymphoma development through the modulation of immune signals. Also, it has been demonstrated that LMP2A-mediated intracellular signaling plays significant roles in epithelial carcinogenesis. On the other hand, it has been demonstrated that EBER, which is expected to form double stranded RNA (dsRNA) structure, triggers a signal transduction from host viral RNA sensors RIG-I and TLR3. Activation of innate immune signals by EBER has been reported to contribute to the pathogenesis of EBV-associated diseases, including cancers.
authors.affiliation: Institute for Genetic Medicine Hokkaido University.
authors.forename: Dai
authors.initials: D
authors.lastname: Iwakiri
mesh_terms: D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology; D008223:Lymphoma / Q000276:immunology* / Q000821:virology*; D012330:RNA, Double-Stranded; D012367:RNA, Viral / Q000502:physiology*; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000502:physiology; D014763:Viral Matrix Proteins / Q000502:physiology*; D017735:Virus Latency / Q000235:genetics
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D014763:Viral Matrix Proteins; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases