Immunology Letters, 38 (1993) 207-214 0165 2478 / 93 / $ 6.00 © 1993 ElsevierSciencePublishers B.V. All rights reserved IMLET 02046 Induction of the lytic viral cycle in Epstein Barr virus carrying Burkitt lymphoma lines is accompanied by increased expression of major histocompatibility complex molecules Livia Di Renzo 1, Javier Avila-Carifio and Eva Klein* Department of Tumor Biology, Karolinska Institutet, S-104 O1 Stockholm, Sweden (Received 19 August 1993; revision received27 September 1993;accepted 30 September 1993) 1. Summary Six Epstein Barr virus (EBV) genome-carrying Burkitt lymphoma (BL) cultures (P3HR-1, Raji, Akata, Daudi, Rael and Jijoye) were induced to enter the lytic cycle. Phorbol esther (TPA), n-bu- tyrate, 5-azacytidine (5AzaC) or anti-IgG were used according to their known inducing capacity on these cell lines. Concomitantly with the ap- pearance of the viral early antigens (EA) in a pro- portion of cells, the expression of major histocom- patibility complex (MHC) class II antigens in- creased in the cultures. On P3HR-1 and Raji cells class I expression also increased. The enhancement of MHC expression corre- lated with the efficiency of induction and re- quired only an early event of the viral iytic cycle. Treatment of 3 EBV-negative lymphoma lines (BJAB, Ramos and BL41) with TPA plus n-buty- rate or 5AzaC did not influence MHC expression. Moreover, BL lines which carry the EBV genome after having been infected in vitro and which can- not be induced for the viral lytic cycle did not change MHC expression after treatment with the Key words: Epstein Barr virus; Lytic cycle; Major histocom- patibility complexexpression *Corresponding author: Eva Klein, Department of Tumor Biol- ogy, Karolinska Institutet, S-10401 Stockholm,Sweden. lpresent address." Dipartimento di Medicina Sperimentale, Universit~i 'La Sapienza', Viale Regina Elena 324, 00161 Rome, Italy. inducing agents. In mixed cultures the allo-stimulatory capacity of induced cells with elevated MHC expression was stronger compared to the untreated ones. 2. Introduction Epstein Barr virus (EBV)-transformed B cells (LCL) and EBV-positive Burkitt lymphomas (BL) carry the viral genome as episomes and only a minority of cells in a culture enters the lytic cy- cle. These cells can be detected by the expression of early antigens (EA) and the viral capsid anti- gen (VCA). While the virus transforms B lymphocytes in vitro with high efficiency and lymphoblastoid cell lines are easily established, EBV-carrying B cell malignancies rarely occur. Thus, in the human species the harmless existence of this ubiquitous transforming virus is ensured by highly efficient control mechanisms. The risk is elevated under immunodeficient conditions [1,2]. Experimental results also suggest that, if not entirely then at least in part, mobilization of immune responses against the virus and against virus genome-carry- ing cells represents the control. The first encounter with EBV is followed by a lifetime virus-carrier state and antibodies against some of the viral structural and viral genome-en- coded proteins are always detected in the serum of such individuals. The antibody levels and low number of virus-carrying B lymphocytes in the blood of healthy individuals do not change [3]. It 207