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J Virol. 1988 February; 62(2): 376-386

Potential progenitor sequences of mink cell focus-forming (MCF) murine leukemia viruses: ecotropic, xenotropic, and MCF-related viral RNAs are detected concurrently in thymus tissues of AKR mice.

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

ABSTRACT

Leukemogenic mink cell focus-forming (MCF) viruses of AKR mice are believed to originate in thymic tissue via recombination between ecotropic, xenotropiclike, and endogenous MCF-related murine leukemia virus (MuLV) sequences. We have previously used a synthetic 16-base-pair MCF env-specific oligomer probe to identify subgenomic MCF-related mRNAs present in the thymus tissues of AKR mice prior to the appearance of full-length (8.4-kilobase [kb]) recombinant MCF viral RNAs (A. S. Khan, F. Laigret, and C. P. Rodi, J. Virol. 61:876-882, 1987). These potential MCF env precursors consisted of 7.2-, 3.0-, and 1.8-kb RNA species. In this study, we have determined the structure of the MCF-related mRNAs on the basis of Northern (RNA) blot hybridization analyses by using 10 different MuLV subgenomic DNA probes, determined the nucleotide sequence of a cloned cDNA segment representing the 3' portion of the 7.2-kb mRNA, and studied the expression of ecotropic and xenotropic MuLV sequences by using env-specific DNA probes. The results indicated that ecotropic, xenotropic, and MCF-related transcripts were constitutively and concurrently expressed exclusively in thymus tissue of 2-month-old AKR mice prior to detection of MCF viral RNAs. We have molecularly characterized these thymic MuLV RNAs, which may participate in formation of recombinant MCF viruses; a novel recombinant ecotropic viral RNA was identified as a putative intermediate in the stepwise generation of leukemogenic MCF MuLVs. We have also described the unique structure of the 6.0-kb MCF-related RNAs which were expressed specifically in liver and kidney tissues of AKR mice; these RNAs contained an upstream non-MuLV transcriptional regulatory element.

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