CHARACTERIZATION OF ENDOGENOUS ECOTROPIC AND XENOTROPIC MURINE LEUKEMIA VIRUSES

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One model of leukemogenesis involves the generation of dualtropic muring leukemia viruses (MuLVs) by molecular recombination between the spontaneously induced ecotropic MuLV and endogenous proviral DNA segments present in the chromosomal DNA of the mouse. Following the recombination event, a dualtropic MuLV may gain entry into a susceptible cell (such as a lymphocyte in the thymus) and, if integration occurs at an appropriate site (near putative oncogene), disease may occur. To study the relationship between dualtropic MuLVs and leukemogenesis, we molecularly cloned 2 dualtropic MuLVs; MCF-13 (thymotropic strain) and MCF-111A (non-thymotropic strain) from chronically infected mink cells. Transfection of these cloned DNAs into mink cells resulted in the production of infectious progeny. Nucleotide sequence analyses showed distinct difference in the long terminal repeats (LTRS) between leukemogenic (MCF-13) and non-leukemogenic (MCF-111A) strain. MCF-111A also had a 12 base deletion (encoding for 4 amino acids) near the 3' end of the pol gene. This information will be used to mutagenize the MCF viral DNAs and test their biological activities. The chloramphenicol acetyl transferase (CAT) gene assay was used to a test for the biological activity of AKR-ecotropic, BALB/c-ecotropic, and NFS-xenotropic LTRs. BALB/c-LTR was devoid of any "CAT" activity whereas NFS and AKR LTRs showed 10% and 3% acetylation, respectively. "CAT" gene constructs are being made with MCF and other endogenous LTRs in attempt to relate the LTRs and their expression of biological activity.