Modes of infection and oncogenesis by the Epstein-Barr virus

The EBV is a human γ-herpesvirus associated with various neoplasms. It is responsible for causing cancers of B, T, and NK cells as well as cells of epithelial origin. Such diversity in target cells and the complicated steps of oncogenesis are perplexing when we speculate about the mechanisms of action of EBV-positive cancers. Here, we first note three common features that contribute to the development and maintenance of EBV-positive cancers: effects of EBV oncogenes, immunosuppression and evasion/exploitation of the immune system, and genetic and epigenetic predisposition/alteration of the host genome. Then, we demonstrate the mechanisms of oncogenesis and the means by which each EBV-positive cancer develops, with particular focus on the mode of EBV infection. The EBV has two alternative life cycles: lytic and latent. The latter is categorized into four programs (latency types 0-III) in which latent viral genes are expressed differentially depending on the tissue of origin and state of cells. The production of viral latent genes tends to decrease with an increase in time, and, in an approximate manner, the expression levels of viral genes are inversely correlated with the degree of abnormalities in the host genome. Occasional execution of the viral lytic cycle also contributes to oncogenesis. Understanding this life cycle of the EBV and its relevance in oncogenesis may provide valuable clues to the development of effective therapies for the associated cancers.