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  • Title: Epstein-Barr virus (EBV) nuclear-antigen-2-induced up-regulation of CD21 and CD23 molecules is dependent on a permissive cellular context.
    Author: Cordier-Bussat M, Billaud M, Calender A, Lenoir GM.
    Journal: Int J Cancer; 1993 Jan 02; 53(1):153-60. PubMed ID: 8416201.
    Abstract:
    The Epstein-Barr virus (EBV) induces unlimited growth of B lymphocytes in vitro, a phenomenon known as immortalization. The elucidation of the mechanisms by which EBV de-regulates B-cell proliferation in vitro will permit an understanding of how the virus contributes in vivo to the genesis of Burkitt's lymphoma (BL) and of lymphoproliferations in immunosuppressed patients. At present, no single EBV immortalizing gene has been identified, and the hypothesis has been made that many viral genes cooperate in establishing an autocrine loop of secretion leading to immortalization. Constitutive expression of B-cell surface molecules such as CD21 and CD23, specifically implicated in the control of B-cell proliferation, is indeed induced at the surface of immortalized B lymphocytes. The expression of the viral nuclear antigen 2 (EBNA2) has been shown to be in part responsible for CD21 and CD23 up-regulation, and EBNA2 is suspected to be a transactivator of cellular genes, although this point remains to be demonstrated. The role of EBNA2 gene, independently of other viral genes, has been investigated by transfection into B-lymphoma lines, but conflicting results have been reported. To further investigate its role in the regulation of CD21 and CD23 molecules, we have compared the effects of EBNA2 expression in 2 sets of B-lymphoma lines infected with P3HR1 EBV strain, and/or transfected with EBNA2 gene. We report here that: (i) EBNA2 expression is not a sufficient condition to induce CD21 and CD23 upregulation, EBNA2's effects are highly dependent on the cellular context, and moreover can be modified by infection with P3HR1 virus; (ii) EBNA2 induces activation of CD23 expression in a very particular way, namely, an increased quantity of CD23 steady-state RNA coding for the form A of the protein, which is not detectable at the cell surface but directly secreted.
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