Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene.

We have determined the sequence of a cloned DNA fragment 1108 base pairs long which corresponds to the 3' end of the Moloney murine leukemia provirus. The clone was obtained as the primary product of reverse transcription and begins with the Moloney "strong stop" sequence, then extends towards the 5' end of the provirus. Our sequence: (i) proves that reverse transcriptase switches templates during minus strand synthesis; (ii) defines the limits of the 515-base-pair repeats which occupy both ends of the integrated provirus; (iii) shows that the structure of the proviral repeats has strong analogy to bacterial insertion sequences, indicating that the Moloney provirus is a transposon; (iv) identifies the putative promotor for genomic transcription within these repeats; (v) shows that the presumed origin of second strand synthesis, which lies just outside the 3' repeat, has tertiary structure analogous to single-stranded bacteriophage origins of replication; (vi) solves the amino acid sequence of most of pI5E, the carboxy-terminal product of the env gene; (vii) allows detailed mapping of the mink cell focus-forming virus substitution locus in a central location within the gp70 region of the env gene; and (viii) identifies a long open translation frame to the right of the env gene (R gene) which could be involved in leukemogenesis.