CHARACTERIZATION OF ENDOGENOUS ECOTROPIC AND XENOTROPIC MURINE LEUKEMIA VIRUSES

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Mink cell focus forming (MCF) viruses are dualtropic murine leukemia viruses (MuLVs) which have been isolated from leukemic mouse tissue. These viruses have been divided into two classes based on their ability to accelerate the onset of thymic lymphomas in AKR mice. Both classes of MCF viruses arise by recombination involving ecotropic MuLV and endogenous MCVF-related env sequences. Leukemogenic MCF MuLVs (class 1) replicate efficiently in the thymus whereas the non-leukemogenic (class II) grow poorly in the thymus. Long terminal repeats (LTRs) have been shown to be involved in tissue-specificity and disease induction associated with leukemogenic MuLVs; also, sequences present in the gag, pol, or env regions have been shown to be necessary for expression of maximum leukemogenicity. To study the sequences of MCF-MULVs involved in viral leukemogenesis, molecularly cloned DNAs of leukemogenic MCF-13 and non-leukemogenic MCF-111A MuLVs were obtained and the nucleotide sequences of the LTRs, 3' pol and 5' env regions determined. The reults of compartive sequence analysis indicated difference in the LTR and 3' pol regions between MCF-13 and MCF-111A MuLV DNAs. The LTR associated with MCF-13 was closely related to that present in xenotropic MuLVs, whereas the LTR sequence of MCF-111A that identical except for 1 bp to the ecotropic proviral LTR. A 12 bp nucleotide stretch, characteristic of leukemogenic MCF MuLVs, was present in MCF2-13 in the 3' pol region but was lacking in MCF-111A. No significant sequence divergence was seen between MCF-13 and MCF-111A MuLV DNAs in the env region. These results suggest that the leukemogenic potential of MCF-13 may reside in LTR and 3' pol sequences.