The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

The nasal type, extranodal natural killer or T(NK/T)-cell lymphoma is usual ly associated with latent Epstein-Barr virus (EBV) infection. In order to e lucidate the EBV gene expression patterns in vivo, we examined eight patien ts with cutaneous EBV-related NK/T-cell lymphomas, including six patients w ith a NK-cell phenotype and two patients with a T-cell phenotype. The impli cation of EBV in the skin lesions was determined by the presence of EBV-DNA , EBV-encoded nuclear RNA (EBER) and a clonality of EBV-DNA fragments conta ining the terminal repeats. Transcripts of EBV-encoded genes were screened by reverse transcription- polymerase chain reaction (RT-PCR), and confirmed by Southern blot hybridization. The expression of EBV-related antigens was examined by immunostaining using paraffin-embedded tissue sections and cel l pellets of EBV-positive cell lines. Our study demonstrated that an sample s from the patients contained EBV nuclear antigen (EBNA)-1 mRNA which was t ranscribed using the Q promoter, whereas both the Q promoter and another up stream promoter (Cp/Wp) were used in EBV-positive cell lines, B95.8, Raji a nd Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was detected in seven of eight patients and all cell lines, whereas EBNA-2 transcripts were found on ly in the cell lines. Immunostaining showed no LMP-1, EBNA-2 or ZEBRA antig ens in the paraffin-embedded tissue sections, although they were positive i n the cell line cells. Latent BHRF1 transcripts encoding bcl-2 homologue an d BCRF1 transcripts encoding viral interleukin (vIL)-10 were detected in on e and two of eight patients, respectively. A patient with NK-cell lymphoma expressing both transcripts died of rapid progression of the illness. Our r esults indicate that the restricted expression of the latency-associated EB V genes and the production of vIL-10 and bcl-2 homologue may favour tumour growth, evading the host immune surveillance. (C) 2001 Cancer Research Camp aign.