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Journal of Virology, March 2000, p. 2793-2803, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Expression of Two Related Viral Early Genes in Epstein-Barr Virus-Associated Tumors

Shao-An Xue,1,dagger Qi-Long Lu,2 R. Poulsom,3 Loraine Karran,1,Dagger M. D. Jones,1 and Beverly E. Griffin1,*

Department of Infectious Diseases (Virology), Imperial College School of Medicine,1 and Clinical Sciences Centre,2 Hammersmith Hospital, London W12 ONN, and ICRF Histopathology Unit, London WC2A 3PX,3 United Kingdom

Received 1 December 1999/Accepted 7 December 1999

The transcription of two early "leftwardly" expressed genes carrying repetitive sequences, IR2 and IR4, has been studied for Epstein-Barr virus-associated tumors, and for established B-cell lines, using sequence-specific probes generated for this purpose. Whereas the IR4 transcript was identified in every tumor and cell line assessed (except B95-8, with a deletion that removes the gene), expression of the IR2 gene was restricted to B lymphocytes. Though the promoters for both transcripts lie within homologous regions (DL and DR) in the viral genome, the IR2 promoter appears more tightly regulated. Detailed characterization of the IR4 transcript from a nasopharyngeal carcinoma tumor, C15, identifies a sequence variant of this gene that differs from those reported for B cells; in situ hybridization methods show transcription to be restricted to a subset of cells, with the strongest signals 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), chemical induction enhanced transcriptional expression of the IR4 gene in the C15 tumor, although staining for both the IR4 antigen and that of the virus 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 and viral lytic replication. Both roles could be fulfilled in the absence of translation.

* Corresponding author. Present address: Viral Oncology Unit, Division of Medicine, ICSM at St. Mary's, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 (0)207 594 3670. Fax: 44 (0)207 402 1037. E-mail: bgriffin{at}ic.ac.uk.

dagger Present address: Viral Oncology Unit, Division of Medicine, Imperial College School of Medicine at St. Mary's, London W2 1PG, United Kingdom.

Dagger Present address: Haddow Laboratories, Institute for Cancer Research, Belmont, Sutton, Surrey SM2 5NG, United Kingdom.

Journal of Virology, March 2000, p. 2793-2803, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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