**2.4.2 EBV transformation**

EBV is associated with a number of human malignancies. There is increasing research interest in the molecular functions of these EBV gene products in transformation and evasion from host immune surveillance systems (Izumi 2001). BAC technology made the study on the molecular function of EBV transforming genes feasible because some latent genes such as EBNA1 cannot be maintained in latently infected B cells using traditional cosmid technology (Izumi 2001; Feederle, Bartlett et al. 2010). EBNA1 was found to function as a transactivator of other latent proteins, and was required for replication of the viral genome (Altmann, Pich et al. 2006). When 71kb of EBV DNA genome was amplified in *E.coli* and transfected into primary B-lymphocyes, Altmann et al (Altmann, Pich et al. 2006) identified that EBV DNA is sufficient to immortalize primary human B lymphocytes. Kempkes et al (Kempkes, Pich et al. 1995; Izumi 2001) also identified EBNA3a as a transforming gene, which contributes primarily to the initiation of cell proliferation (Kempkes, Pich et al. 1995; Izumi 2001). Two genes BALF1 and BHRF1 which encode homologous cellular antiapoptotic viral Bcl-2 proteins (vBcl-2), were suggested to interfere with the cell apoptosis program to counteract cell death, which protects the virus from apoptosis in its host cell during virus synthesis (Altmann and Hammerschmidt 2005).
