title: Role of Epstein-Barr virus in Burkitt's lymphoma.
abstract: We established an in vitro system representing BL-type EBV infection, which is characterized by expression of EBNA1, EBER, BARF0, and LMP2A, and absence of EBNA2 and LMP1 expression (Shimizu et al. 1994; Komano et al. 1998). Comparison of EBV-positive and -negative Akata cell clones revealed that EBV contributes to the malignant phenotype and resistance to apoptosis. This is clear evidence that EBV is not a passenger and plays a role in BL. Moreover, we found that EBERs are responsible for these phenotypes (Komano et al. 1999). In the transfection study, EBER-expressing Akata cell clones restored the malignant phenotype, resistance to apoptosis and upregulated expression of bcl-2 protein to a level comparable to the restoration rate of EBER expression compared with EBV-reinfected cell clones. Many RNAs are known to have catalytic functions; however, there has been no report describing an oncogenic RNA. This is the first paper that provides evidence that RNA polymerase III-transcribed virus-encoded small RNAs affect the malignant phenotype and resistance to apoptosis. Like Akata cells (Takada et al. 1991), all the BL cells possess a chromosomal translocation involving the c-myc locus, which results in constitutive activation of the c-myc gene (Klein 1981). In mammalian cells, deregulated expression of c-myc has been shown to contribute not only to tumorigenesis (Land et al. 1983) but also to induce apoptosis (Askew et al. 1991; Evan et al. 1992; Milner et al. 1993). Therefore, BL cells are predisposed to c-myc-induced apoptosis. Our data imply that EBV infection would upregulate expression of bcl-2 protein to protect cells from c-myc-induced apoptosis, and to allow c-myc to exert its oncogenic functions (Vaux et al. 1988; Brito-Babapulle et al. 1991; Bissonnette et al. 1992; Fanidi et al. 1992; Karsan et al. 1993; Mohammad et al. 1993; Oltvai et al. 1993; Marin et al. 1995). In this way bcl-2 might cooperate with c-myc in the development of BL (Fig. 5).
authors.affiliation: Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takada
mesh_terms: D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000473:pathology* / Q000821:virology*; D018929:Cell Culture Techniques; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D012367:RNA, Viral / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral