title: EBV lytic infection enhances transformation of B-lymphocytes infected with EBV in the presence of T-lymphocytes.
abstract: Epstein-Barr virus (EBV) establishes lifelong latency in B-lymphocytes following infection. Although in immune-competent individuals EBV remains in a quiescent state, in immunodeficient individuals, such as those with AIDS or transplant recipients, B-lymphocytes infected with EBV proliferate to give rise to lymphoproliferative diseases. Similarly, in vitro, EBV transforms human B-lymphocytes into indefinitely growing lymphoblastoid cell lines (LCLs) in the absence of cytotoxic T-lymphocytes. Although LCLs harbor the entire EBV genome as an episome, in most cells the virus remains in a latent state expressing a fraction of EBV genes, and lytic infection occurs spontaneously but only in a small percentage of cells. Here, we report that lytic infection contributes to EBV-induced lymphoproliferation by a paracrine mechanism. An EBV immediate-early protein, BZLF1, induces IL-13, thus facilitating the proliferation of EBV-transformed B-lymphocytes in the presence of T-lymphocytes. These data suggest that lytic gene products could contribute to virus-induced oncogenesis by a paracrine mechanism.
authors.affiliation: Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Koichi Ricardo
authors.initials: KR
authors.lastname: Katsumura
authors.forename: Seiji
authors.initials: S
authors.lastname: Maruo
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D019899:Paracrine Communication; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018793:Interleukin-13; D015534:Trans-Activators; D014763:Viral Matrix Proteins