EPSTEIN-BARR-VIRUS LATENT GENE-EXPRESSION IN PRIMARY EFFUSION LYMPHOMAS CONTAINING KAPOSIS-SARCOMA-ASSOCIATED HERPESVIRUS HUMAN-HERPESVIRUS-8

Primary effusion (body cavity-based) lymphoma (PEL) is a recently reco gnized subtype of malignant lymphoma that exhibits distinctive clinica l and biological features, most notably its usual infection with the K aposi's sarcoma-associated herpesvirus (KSHV). The vast majority of ca ses also contain Epstein-Barr virus (EBV). This dual viral infection i s the first example of a consistent dual herpesviral infection in a hu man neoplasm and provides a unique model to study viral interactions. We analyzed the pattern of EBV latent gene expression to determine the pathogenic role of this agent in PELs, We examined five PELs coinfect ed with EBV and KSHV by reverse transcription-polymerase chain reactio n (RT-PCR), in situ hybridization, and immunohistochemistry, EBER1 mRN A, a consistent marker of viral latency, was positive in all PEL cases , although at lower levels than in the non-PEL controls due to EBER1 e xpression by only a variable subset of lymphoma cells. Op-initiated mR NA, encoding only EBNA1 and characteristic of latencies I and II, was positive in all PEL cases, Wp- and Cp-initiated mRNAs, encoding all EB NAs and characteristic of latency III, were negative in all cases. LMP 1 mRNA, expressed in latencies II and III, was present in three cases of PEL, although at very low levels that were not detectable at the pr otein level by immunohistochemistry. Low levels of LMP2A mRNA were det ected in all cases. BZLF1, an early-intermediate lytic phase marker, w as weakly positive in four cases, suggesting a productive viral infect ion in a very small proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore, PELs exhibit a restricted latency patte rn, with expression of EBNA1 in all cases, and low LMP1 and LMP2A leve ls. (C) 1997 by The American Society of Hematology.