A retrovirus from human leukemia cell lines: its isolation, characterization, and implication in human adult T-cell...

We have tried to isolate a retrovirus from adult T-cell leukemia (ATL) which is a new clinical entity of T-cell malignancy. This disease shows a peculiar geographic clustering of patient birthplaces in the southwestern part of Japan. A retrovirus was isolated from the T-cell line, MT-2, which was established from cord lymphocytes cocultivated with leukemic cells from an ATL patient and characterized by: (a) density of 1.152-1.155 g/ml in sucrose gradient; (b) reverse transcriptase activity; (c) specific protein components; (d) RNA labeled with 3H-uridine, and (e) specific DNA complementary with viral RNA. The retrovirus was named adult T-cell leukemia virus (ATLV). Complementary DNA (cDNA) prepared by the endogenous reaction of detergent-treated virions hybridized with 35S RNA in MT-2 cells and another ATL cell line, MT-1, and this 35S RNA was inducible with IUDR treatment of the MT-1 cells, indicating that ATLV is a typical retrovirus containing 35S RNA as the genome. However, the cDNA did not show any detectable hybridization with cellular RNA of other human cell lines unrelated to ATL. The ATLV proviral DNA was detected in the chromosomal DNA of MT-1 and MT-2 cell lines as well well as in fresh peripheral blood cells of all five patients with ATL tested; however, it was not found in those of three healthy adults. Furthermore, sera from the patients reacted with one component of the ATLV protein, but normal sera did not. These sera and all other sera from ATL patients were previously shown to react with antigen(s) in leukemic cells of ATL, and the antigen(s) also reacted with sera from about 25% of the healthy adults in the endemic area, but not in the non-endemic area. These close associations of ATLV proviral DNA and proteins with ATL are direct evidence strongly suggesting the involvement of the retrovirus, ATLV, in the leukemogenesis of human ATL.