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Sustained Expression of the Novel EBV-Induced Zinc Finger Gene, ZNF^EB, Is Critical for the Transition of B Lymphocyte Activation to Oncogenic Growth Transformation¹

Division of Infection, Immunity, Injury, and Repair, The Hospital for Sick Children, Toronto, Ontario, Canada

EBV is a human tumor virus that infects and establishes latency in the majority of humans worldwide. In vitro, EBV growth transforms primary B lymphocytes into lymphoblastoid cell lines with high efficiency. We have used cDNA subtraction cloning to identify cellular target genes required for growth transformation and identified a new C₂H₂ (Krüppel-type) zinc finger gene, ZNF^EB, that is trans-activated early following EBV infection. In this study, we characterize ZNF^EB, including its intronless locus, and human and mouse protein variants. The gene is transiently expressed during normal lymphocyte activation, and its expression is sustained in EBV-positive but not EBV-negative B cell lines. There is limited expression in nonhemopoietic tissues. Its critical role in the growth transformation of B lineage cells is indicated by the abrogation of transformation with antisense strategies. ZNF^EB maps to chromosome 18q12, a region with mutations in numerous, predominantly hemopoietic malignancies.

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