Molecular biology of EBV in relationship to AIDS-associated oncogenesis

Epstein-Barr virus (EBV) is a gammaherpesvirus of the Lymphocryptovirus genus, which infects greater than 90% of the world's population. Infection is nonsymptomatic in healthy individuals, but has been associated with a number of lymphoproliferative disorders when accompanied by immunosuppression. Like all herpesviruses, EBV has both latent and lytic replication programs, which allows it to evade immune clearance and persist for the lifetime of the host. Latent infection is characterized by replication of the viral genome as an integral part of the host cell chromosomes, and the absence of production of infectious virus. A further layer of complexity is added in that EBV can establish three distinct latency programs, in each of which a specific set of viral antigens is expressed. In most malignant disorders associated with EBV, the virus replicates using one of these three latency programs. In the most aggressive latency program, only 11 of the hitherto 85 identified open reading frames in the EBV genome are expressed. The other two latency programs express even smaller subsets of this repertoire of latent genes. The onset of the AIDS pandemic and the corresponding increase in individuals with acquired immunodeficiency resulted in a sharp increase in EBV-mediated AIDS-associated malignancies. This has sparked a renewed interest in EBV biology and pathogenesis.