Epstein-Barr virus latent gene expression in primary effusion lymphomas containing Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8.

TitleEpstein-Barr virus latent gene expression in primary effusion lymphomas containing Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8.
Publication TypeJournal Article
Year of Publication1997
AuthorsHorenstein MG, Nador RG, Chadburn A, Hyjek EM, Inghirami G, Knowles DM, Cesarman E
Date Published1997 Aug 01
KeywordsAdult, Aged, DNA-Binding Proteins, Epstein-Barr Virus Nuclear Antigens, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Viral, Herpesviridae Infections, Herpesvirus 4, Human, Herpesvirus 8, Human, Humans, In Situ Hybridization, Lymphoma, AIDS-Related, Lymphoma, Non-Hodgkin, Male, Polymerase Chain Reaction, RNA Splicing, RNA, Messenger, RNA, Neoplasm, RNA, Viral, Trans-Activators, Tumor Cells, Cultured, Tumor Virus Infections, Viral Matrix Proteins, Viral Proteins, Virus Latency

Primary effusion (body cavity-based) lymphoma (PEL) is a recently recognized subtype of malignant lymphoma that exhibits distinctive clinical and biological features, most notably its usual infection with the Kaposi's sarcoma-associated herpesvirus (KSHV). The vast majority of cases also contain Epstein-Barr virus (EBV). This dual viral infection is the first example of a consistent dual herpesviral infection in a human 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 coinfected with EBV and KSHV by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. EBER1 mRNA, 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 expression by only a variable subset of lymphoma cells. Qp-initiated mRNA, encoding only EBNA1 and characteristic of latencies I and II, was positive in all PEL cases. Wp- and Cp-initiated mRNAs, encoding all EBNAs and characteristic of latency III, were negative in all cases. LMP1 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 protein level by immunohistochemistry. Low levels of LMP2A mRNA were detected in all cases. BZLF1, an early-intermediate lytic phase marker, was weakly positive in four cases, suggesting a productive viral infection in a very small proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore, PELs exhibit a restricted latency pattern, with expression of EBNA1 in all cases, and low LMP1 and LMP2A levels.

Alternate JournalBlood
PubMed ID9242551
Grant ListCA68939 / CA / NCI NIH HHS / United States
EY06337 / EY / NEI NIH HHS / United States
Related Faculty: 
Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.

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