Cloning of the MCF1233 murine leukemia virus and identification of sequences involved in viral tropism, oncogenicity and T cell epitope formation.

MCF1233 is an oncogenic C57BL-derived retrovirus of the Murine Leukemia Virus (MuLV) family, that causes T and B lymphomas in an MHC-associated fashion. In this study, we cloned MCF1233, determined its nucleotide sequence and, by comparison with its MuLV relatives, identified the sequences that relate to the leukemogenic character of this virus. MCF1233 was found to have an ecotropic backbone, and carried acquired polytropic sequences in the 3' pol and 5' env region. The gag-region contained six specific nucleotides, determining the viral B-tropism. Short sequences within the U3 LTR shared specific homology with the xenotropic Bxv-1 MuLV, which is the U3 donor for leukemogenic MCF MuLV of AKR origin. These sequences, in combination with specific ecotropic sequences present in env p15E, most likely determine the viral oncogenicity. Currently, the deduced MCF1233 amino sequence is being exploited for T cell epitope analysis, which in this paper is discussed with respect to antigenically distinct Friend/Moloney/Rauscher types of MuLV. Identification of these T cell epitopes will contribute to our understanding of the fundamental aspects of immune control on MCF1233-induced lymphomagenesis. It will help to elucidate the mechanisms that underlie immune escape of T lymphomas, rarely arising in immunoresistant mice, and allow the development of vaccination protocols for tumor therapy.