LATENT MAREKS-DISEASE VIRUS CAN BE ACTIVATED FROM ITS CHROMOSOMALLY INTEGRATED STATE IN HERPESVIRUS-TRANSFORMED LYMPHOMA-CELLS

Marek's disease virus (MDV), a lymphotropic herpesvirus, induces T-cel l lymphomas in chicken, its natural host. The lymphoma cells are laten tly infected with MDV but the viral contribution to the transformed ph enotype is not understood. To investigate the virus-cell interaction, we focused on the status of MDV in the transformed cells. By the use o f highly sensitive fluorescent in situ hybridization with metaphase ch romosomes, we found (i) MDV DNA to be randomly integrated at multiple sites in the chromosomes of primary lymphoma cells from chicken tissue s; (ii) extrachromosomal, circular MDV genomes were absent and linear virion DNA was usually not detectable in the latently infected lymphom a cells (iii) the pattern of integration sites revealed the clonal ori gin of the tumour cells; which (iv) was retained in in vitro establish ed cell lines derived from primary lymphomas; (v) activation of the ly tic phase of MDV's life cycle occurred in vitro suggesting that MDV ca n escape from its integrated status by an unknown mechanism.