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In this study, we investigated the presence of Epstein–Barr virus (EBV) in liver tissue from 35 patients with hepatocellular carcinoma (HCC). EBV DNA was detected in 13 patients (37%) by Southern blot hybridization. In 10 of these patients, EBV DNA was present in tumor tissue only, whereas in the other 3, it was detected in both tumor and nontumor tissues. The quantity of EBV DNA detected was equivalent to 1–10 viral DNA molecules/100 cells. EBV-determined nuclear antigen was detected in 7–13% of the carcinoma cells in three tumor tissue samples that contained approximately one copy of the EBV genome/10 cells. A single terminal fragment of EBV DNA was identified in these tissues, suggesting that the EBV-infected cells in HCC represent clonal proliferation. Western blotting and reverse transcription–polymerase chain reaction analyses demonstrated that these three tumor tissue specimens were positive for EBV-determined nuclear antigen 1 and BamHI A transcripts but were negative for the other latent EBV products, including EBV-encoded small RNA. The results indicated that there is a high EBV load in HCC tissue and that all of the HCC tissue examined showed a novel pattern of EBV latency characterized by absence of EBV-encoded small RNA expression.

To elucidate the association of Epstein-Barr virus (EBV) and salivary gland tumors, 114 cases of tumors of major salivary glands were investigated. EBV DNA was detected in all 6 cases of undifferentiated carcinoma and all 3 cases of T-cell lymphoma, but not in other tumor tissues. In situ hybridization studies for EBV DNA and EBV-encoded small RNA 1 (EBER1) showed specific localization of the EBV sequences to the undifferentiated carcinoma cells and T-lymphoma cells. Moreover, intense DNA signals were detected on nonneoplastic epithelial cells of T-lymphoma tissues. These epithelial cells were negative for EBER1 and expressed BZLF1, BALF2, and gp350/220 proteins associated with virus production. In contrast, nonmalignant epithelial cells surrounded by undifferentiated carcinoma cells showed no evidence of EBV infection or virus replication. These results indicate that there is an unusual association of salivary gland T-cell lymphomas with lytic EBV replication of nonmalignant epithelial cells.