Human adult T-cell leukemia virus: molecular cloning of the provirus DNA and the unique terminal structure.

Abstract

Adult T cell leukemia virus (ATLV) is a human retrovirus closely associated with adult T cell leukemia. The integrated provirus DNA and c[complementary]DNA from virion RNA were moleculary cloned and their structures were analyzed. Clone .lambda.ATM-1 of an integrated provirus DNA in the MT-1 cell line, established from adult T cell leukemia cells by cocultivation with cord lymphocytes, contained DNA .apprx. 13,000 base pairs (bp) long and long terminal repeats (LTR) at both ends of the viral sequence that were .apprx. 8000 bp long. These 2 LTR sequences were linked to cellular sequences with direct repeats of 7 bp. Each LTR consisted of 754 bp including inverted repeats of 2 bp at the ends and the T-A-T-A-A box, characteristics in common with those of LTR of other known retroviruses. Adjacent to the 5'' LTR there was a sequence identical to the tRNAPro binding site in murine leukemia virus, suggesting that tRNAPro is a primer for reverse transcription of the viral genome. From these structural features, the mechanism of ATLV replication was suggested to be the same as that of other known animal retroviruses. The length of the small terminal repeats at the ends of the RNA genome, 228 .+-. 1 bases, is much longer than the lengths, up to 80 bases, of those in avian, mouse or primate retroviruses so far analyzed. These findings suggest that ATLV should be classified in a distinct group of retroviruses with bovine leukemia virus which also makes unusually long strong-stop cDNA.