The epstein‐barr virus latent membrane protein‐1 (LMP1) induces interleukin‐10 production in burkitt lymphoma lines

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Abstract
Human interleukin‐10 (h‐IL‐10) is a pleiotropic cytokine with stimulatory activity on B‐Iymphocytes. Recent evidence indicates that infection with Epstein‐Barr virus (EBV) induces h‐IL‐10 production in B‐cells and that this cytokine may contribute to EBV‐induced B‐cell transformation. It is not known whether h‐IL‐10 induction by EBV correlates with distinct phenotypic features of the infected cells or with the expression of particular viral genes. We have approached these questions by investigating the expression of h‐IL‐10 mRNA in a panel of B‐cell lines including: in vitro EBV‐transformed lymphoblastoid cell lines (LCLs), EBV‐carrying Burkitt lymphoma (BL) lines, EBV‐negative BL lines and their sublines infected with different EBV strains, or transfected with the transformation‐associated viral gene. h‐IL‐10 mRNA was detected by reverse‐transcriptase‐assisted (RT)‐PCR in a subset of EBV‐negative BLs and in all FBV‐positive BL lines and LCLs investigated except Daudi. This cell line carries an EBV nuclear antigen (EBNA)‐2 gene‐defective virus strain. h‐IL‐10 mRNA was induced by conversion of 3 EBV‐negative and h‐IL‐10‐negative BL lines (BL41, BL47 and BL49) with the transforming, B95.8‐derived EBV strain. P3HR‐1 virus convertants that do not express the viral EBNA‐2 and the EBV latent membrane protein (LMP)‐1, and fail to progress towards a LCL‐like cell phenotype, showed no evidence of h‐IL‐10 up‐regulation. Expression of LMP1 was sufficient to induce h‐IL‐10 mRNA in transfected sublines of the EBV‐negative DG75 and BL41 cell lines, whereas expression of EBNA1, 2, 5 or 6 had no effect. h‐IL‐10 was detected in the culture supernatants of the LMP1 transfectants by specific ELISA assays. The present findings confirm the role of LMP1 in the transactivation of a wide variety of cellular genes which may be involved in EBV‐induced B‐cell transformation.

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