How does Epstein–Barr virus (EBV) complement the activation of Myc in the pathogenesis of Burkitt's lymphoma?

A defining characteristic of the aggressive B cell tumour Burkitt's lymphoma (BL) is a reciprocal chromosomal translocation that activates the Myc oncogene by juxtaposing it to one of the immunoglobulin gene loci. The consequences of activating Myc include cell growth and proliferation that can lead to lymphomagenesis; however, as part of a fail-safe mechanism that has evolved in metazoans to reduce the likelihood of neoplastic disease, activated oncogenes such as Myc may also induce cell death by apoptosis and/or an irreversible block to proliferation called senescence. For lymphoma to develop it is necessary that these latter processes are repressed. More than 95% of a subset of BL – known as endemic (e)BL because they are largely restricted to regions of equatorial Africa and similar geographical regions – carry latent Epstein–Barr virus (EBV) in the form of nuclear extra-chromosomal episomes. Although EBV is not generally regarded as a driving force of BL cell proliferation, it plays an important role in the pathogenesis of eBL. Latency-associated EBV gene products can inhibit a variety of pathways that lead to apoptosis and senescence; therefore EBV probably counteracts the proliferation-restricting activities of deregulated Myc and so facilitates the development of BL.