EBV MicroRNAs in Primary Lymphomas and Targeting of CXCL-11 by ebv-mir-BHRF1-3

Abstract

EBV-encoded microRNAs (miRNAs) have been identified and their functions are being studied. The expression pattern of these miRNAs in clinical samples of EBV-associated non-Hodgkin's lymphomas is unknown. We analyzed five primary "endemic" pediatric Burkitt's lymphomas (BL), two acquired immunodeficiency syndrome (AIDS)-related type I latency BL lines, a type III latency line, three EBV(+) primary effusion lymphomas (PEL), and three AIDS-related diffuse large B-cell lymphomas (DLBCL) for expression of EBV-encoded miRNAs. A markedly elevated expression of miRNA BHRF1-3 in type III relative to its parental type I BL line was found. Primary unmanipulated type I BLs and EBV(+) PELs expressed high levels of BART2 miRNA, whereas DLBCLs expressed both BART2 and BHRF1-3 species. BHRF1-3 miRNA expression inversely correlated with levels of a putative cellular target, the IFN-inducible T-cell attracting chemokine CXCL-11/I-TAC, and suppression of this factor was reversed by transfection of an antisense oligo to the EBV miRNA BHRF1-3. EBV-encoded miRNAs are expressed in primary lymphomas classically linked to the virus and are associated with the viral latency status. Targeted suppression of CXCL-11/I-TAC by a viral-encoded miRNA may serve as an immunomodulatory mechanism in these tumors.