EPSTEIN-BARR-VIRUS REPLICATION IN HODGKIN S-DISEASE

Epstein-Barr virus (EBV) is present in up to 40% of Hodgkin's disease (HD). The viral genomes remain latent within Reed-Sternberg cells (RS cells), but the recent detection of Zebra protein in rare neoplastic c ells of a few EBV+ HD cases, suggests an activation of EBV replication . We have studied fifty HD cases containing EBV genomes and expressing LMP1 protein (including five AIDS-related cases), by immunohistochemi stry with anti-Zebra antibodies. Four of these cases (all HIV-) showed Zebra+ tumor cells. One of these four cases showed numerous Zebra+ ne oplastic cells (approximately 1 % of tumor cells) and positive stainin g for EA-R protein, thus indicating early gene expression. In situ hyb ridization with biotinylated BamHI W probe revealed in this case, a si gnal of unusual strength within some Reed-Sternberg cells, probably re lated to increased number of EBV genomes, thus suggesting EBV replicat ion. Viral replication was finally confirmed in this case, by the dete ction of BLLF1 transcripts (encoding for the membrane antigen gp 35012 20) using reverse transcriptase and polymerase chain reaction. Thus, a very few Zebra+ neoplastic cells are concerned by viral replication, most of them harboring EBV involved in an abortive, instead of a full lytic cycle. EBV replication in RS cells remains an exceptionnal event , but may provide clues to immunologic mechanisms of control of viral latency. Clinical implications need further investigations.