Activation of a novel KpnI transcript by downstream integration of a human T-lymphotropic virus type I provirus

Abstract

A cDNA library was constructed from the HUT102 cell line established from a patient with adult T-cell leukemia/lymphoma and screened for cDNA clones that contain (i) cellular sequences abundantly expressed in HUT102 cells and not in the virus-negative T-cell line HUT78, and (ii) viral long terminal repeat (LTR) sequences either in the 5' end or in the 3' end. One such cDNA clone, KT1, was isolated and its nucleotide sequence was determined. It contains three regions: a KpnI repeat, a unique cellular region (UCR), and the U3 + R sequence of the human T-lymphotropic virus type I LTR. The arrangement of this clone suggests that its RNA transcript was activated by provirus integration in cis, possibly by the activity of a downstream provirus enhancer. Analysis of HUT102 DNA shows that one allele of the KT1 UCR is rearranged. The expression of the KT1 UCR is unique to HUT102. These data are consistent with the idea that the human T-lymphotropic virus type I LTR contains an enhancer which can activate upstream sequences in cis. The possible significance of this finding is discussed.