COMPLEX NATURE OF THE MAJOR VIRAL POLYADENYLATED TRANSCRIPTS IN EPSTEIN-BARR VIRUS-ASSOCIATED TUMORS

The most abundant polyadenylated viral transcripts in the Epstein-Barr virus (EBV)-associated tumor nasopharyngeal carcinoma are a family (a pparent sizes, 4.8, 5.2, 6.2, and 7.0 kb) of highly spliced cytoplasmi c RNAs ''pressed from the BamHI-I and -A regions of the viral genome i n an antisense direction with respect to several viral lytic functions encoded within the same region and concerned with the lytic cycle of the virus. We have called these complementary-strand transcripts. They are also expressed in B cells, including Burkitt's lymphoma and EBV-i mmortalized marmoset cell lines, and tumors generated in cottontop tam arins in response to EBV infection, but at a lower level. The complete structure of the major 4.8-kb RNAs (seven or eight exons) was determi ned in this study; the larger, but related, transcripts appear to be p roduced by differential splicing. The transcriptional promoter for the major complementary-strand transcripts, located in BamHI-I, contains several well-characterized transcriptional control elements (E2A, SP1, and AP1) and is functionally active in both B lymphocytes and epithel ial cells. It appears to be a bifunctional viral promoter, as it also contains the initiation codon for a gene (BILF2) that encodes a glycop rotein that is expressed off the other strand. Splicing events create a number of small AUG-initiated open reading frames, one of which has homology to functionally significant regions of the EBV-encoded nuclea r antigen 2 and to E2 (in papillomavirus). The complex nature of these transcripts and their potential role in the virus association with ma lignancy are considered.