title: 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.
authors.affiliation: The Viral Oncology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Tianli
authors.initials: T
authors.lastname: Xia
authors.forename: Andrea
authors.initials: A
authors.lastname: O'Hara
authors.forename: Iguaracyra
authors.initials: I
authors.lastname: Araujo
authors.forename: Jose
authors.initials: J
authors.lastname: Barreto
authors.forename: Eny
authors.initials: E
authors.lastname: Carvalho
authors.forename: Jose Bahia
authors.initials: JB
authors.lastname: Sapucaia
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramos
authors.forename: Estela
authors.initials: E
authors.lastname: Luz
authors.forename: Celia
authors.initials: C
authors.lastname: Pedroso
authors.forename: Michele
authors.initials: M
authors.lastname: Manrique
authors.forename: Ngoc L
authors.initials: NL
authors.lastname: Toomey
authors.forename: Carlos
authors.initials: C
authors.lastname: Brites
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
authors.forename: William J
authors.initials: WJ
authors.lastname: Harrington
mesh_terms: D001706:Biopsy; D045744:Cell Line, Tumor; D054371:Chemokine CXCL11 / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D008223:Lymphoma / Q000378:metabolism* / Q000821:virology*; D035683:MicroRNAs / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D012260:Ribonucleases / Q000378:metabolism; D014162:Transfection; D016896:Treatment Outcome; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency
chemical_list: C083278:BHRF1 protein, Human herpesvirus 4; C515202:CXCL11 protein, human; D054371:Chemokine CXCL11; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D014764:Viral Proteins; D012260:Ribonucleases