Expression of two related viral early genes in Epstein-Barr virus-associated tumors

The transcription of two early "leftwardly" expressed genes carrying repeti tive sequences, IR2 and IR4, has been studied for Epstein-Barr virus-associ ated tumors, and for established B-cell lines, using sequence-specific prob es generated for this purpose. Whereas the IR4 transcript was identified in every tumor and cell line assessed (except B95-8, with a deletion that rem oves the gene), expression of the IR2 gene was restricted to B lymphocytes. Though the promoters for both transcripts lie within homologous regions (D -L and D-R) in the viral genome, the IR2 promoter appears more tightly regu lated. Detailed characterization of the IR4 transcript from a nasopharyngea l carcinoma tumor, C15, identifies a sequence variant of this gene that dif fers from those reported for B cells; in situ hybridization methods show tr anscription to be restricted to a subset of cells, with the strongest signa ls seen adjacent to host stroma. As with B cells in culture (Y. Gao, P. R. Smith, L. Karran, Q. L. Lu, and B, E. Griffin, J. Virol. 71:84-94, 1997), c hemical induction enhanced transcriptional expression of the IR4 gene in th e C15 tumor, although staining for both the IR4 antigen and that of the vir us lytic switch, Zta, gave negative results. In a Burkitt's lymphoma biopsy specimen, however, both proteins were found expressed, notably in the same subset of cells. The data here and elsewhere (Gao et al., J. Virol., 1997) are consistent with a block to intracellular transport of the transcript(s ) and suggest nuclear roles for it in tumors, possibly in RNA processing an d viral lytic replication. Both roles could be fulfilled in the absence of translation.