The Molecular Basis of Avian Retrovirus-Induced Leukemogenesis

There is overwhelming evidence that infection by retroviruses can lead to transformation of the infected cell and to tumor development in the target organ of the host. However, the mechanism by which virus-induced oncogenic transformation occurs is not clearly understood. The viral tumorigenesis involves several steps, including infection by the virus, integration of provirus, transformation of the target cells, tumor development, and in some cases metastasis. In an attempt to gain insight into the molecular mechanism of this process, we have studied the avian leukosis virus [(ALV) e.g., RAV-1] induced lymphoid leukosis (LL) by following the fate of proviral DNA of infecting virus through preleukosis, leukosis, and metastasis stages. The results of these studies presented below have indicated that there are multiple sites in the cellular genome of the target tissue where the proviral DNA of infecting virus can integrate, that there may be a few preferred sites at which integration can lead to tumor formation, that deletions and other structural alterations in the proviral DNA may facilitate tumorigenesis, that origin of LL tumors is clonal, and finally that metastasis arise by migration of a primary clone to the secondary site.