Function (s) of a novel Epstein-Barr virus latent gene, BARF0

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Epstein-Barr virus (EBV) is closely associated with a B-cell tumor, Burkitt's lymphoma, and epithelial tumors, nasopharyngeal carcinoma and gastric carcinoma (GC). Among the known latent EBV genes, only a limited number of them, e.g. EBNA1, EBERs, LMP2A and recently identified BARF0, are expressed in the EBV-associated human malignancies. However, the function (s) of BARF0 is still unclear, whereas those of EBNA1, EBERs and LMP2A are being clarified. We investigated the possible role (s) of BARF0 in cellular malignant change by using the useful in vitro epithelial infection system by EBV, which we developed before.Expression plasmids for EBNA1, EBERs, BARF0, RK-BARF0 and LMP2A were introduced independently into a cultured normal gastric epithelial cell, PGE-5 (J.Virol., 73 : 1286-92, 1999), and its cell clones expressing each gene were isolated by drug selection. Among those clones, BARF0- and RK-BARF0-expressing clones showed a significantly higher clonability in agar than EBNA1-, EBER-, LMP2A- and neo^r gene-transfected ones, though lower than EBV-infected counterparts. Another examination showed that, in many EBV-infected cell lines and biopsies from GC and NPC tissues, BARF0 was consistently expressed at the much higher level than RK-BARF0. Taken together, these results suggest that BARF0 has oncogenic potential, at least partially, for human gastric epithelial cells. Additionally, since the malignant phenotype seen in EBV-infected PGE-5 cells was not fully reproduced by BARF0 alone, other unidentified EBV latent gene (s) responsible for epithelial malignant change may exist.