Epstein-Barr virus infection in humans: from harmless to life endangering virus-lymphocyte interactions.

After the primary infection, that may or may not cause infectious mononucleosis, the ubiquitous Epstein-Barr virus (EBV) is carried for lifetime. The great majority of adult humans are virus carriers. EBV was discovered in a B-cell lymphoma (Burkitt lymphoma). EBV infection in humans is the example for the power of immune surveillance against virus transformed, potentially malignant cells. Although the virus can transform B lymphocytes in vitro into proliferating lines, it induces malignancy directly only in immunosuppressed hosts. EBV-induced growth transformation occurs only in B lymphocytes. It is the result of a complex interaction between virally encoded and cellular proteins. Different forms of the virus-cell and the cell-host interactions have evolved during a long period of coexistence between the virus and all Old World (but not New World) primates. The asymptomatic carrier state is based on a viral-strategy that downregulates the expression of the transforming proteins in the virus-carrying cell. In addition to the silent viral-gene carriers and the expressors of the nine virus-encoded genes that drive the growth program, virus carrying cells exist that show other patterns of gene expression, depending on the differentiated state of the host cell. Certain combinations contribute to malignant transformation, but only in conjunction with additional cellular changes. These are induced by direct or cytokine-mediated interactions with normal cells of the immune system.