H-103 Speaking in honor of Peter Vogt: The Epstein-Barr Virus, a 50 year Odyssey

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The epstein - Barr Virus (EBV), is the first human tumor virus identified and is strongly associated with endemic Burkitt’s Lymphoma (BL) in Africa. It is causative agent of the B-cell lymphomas that arise in innate and acquired immunocompromised persons. It is also causative in hairy leukoplakia and infectious mononucleosis. Notably, it is almost certainly causative in the malignancy that originates in epithelial tissue in Waldeyer’s Ring in the Fossa of Rosenmuller of the posterior nasopharynx (NPC). EBV is invariably present in NPC world-wide, whether sporadic or endemic in incidence.

We focused first (1971) on detection of EBV DNA in BL tissue with a highly sensitive cRNA-DNA assay that permitted precise quantitation of number of EBV genomes in tissue extracts.

Later we used this probe for in-situ hybridization studies in BL cells and also in NPC tissues, as well as for detection of EBV in oropharyngeal epithelial cells obtained from students with infectious mononucleosis. The findings also showed that EBV replicated initially in normal human epithelial cells.

Additionally we recognized earlier that the EBV genome could exist in cells in supercoiled episomal form, as well as the linear format found in virus. The EBV episome is the molecular basis for latent EBV infections.

Achievements that followed were characterization of the viral DNA polymerase and understanding its interaction with antiviral drugs. Studies with new antiviral drugs are continuing.

The landmark discovery of IRF7 (1997), the seventh human interferon regulatory factor discovered, was later recognized as the essential common regulator of the expression of Type 1 interferons. Mechanisms of induction of invasion, metastasis and angiogenesis induced by the principal EBV oncoprotein, LMP-1, have now spanned 20 years and remain a main focus.

Current work addresses ubiquitin systems that involve EBV, in particular its deubiquitinating enzyme, and its involvement in mechanisms of DNA repair, EBV immortalization of B-cells, and the genesis of human B-cell lymphomas in humanized mice..

The fascinations of EBV and how it works continue!

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