Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease.

Abstract

A retrovirus (ATLV [adult T-cell leukemia retrovirus]) was unequivocally demonstrated in human adult T cell leukemia (ATL) cell lines by density (1.152-1.155 g/cm3) in a sucrose gradient, reverse transcriptase activity insensitive to actinomycin D, RNA labeled with [3H]uridine and specific proteins with MW of 11,000, 14,000, 17,000, 24,000 and 45,000. Complementary[c]DNA prepared by endogenous reaction with detergent-treated virions hybridized to 35S RNA containing poly(A), which was inducible by IdUrd [iododeoxyuridine] treatment of a T-cell line derived from leukemic cells of the ATL, and the integrated form of ATLV proviral DNA was detected in T-cell lines derived from ATL. The ATLV proviral DNA was also detected in fresh peripheral lymphocytes from all 5 patients with ATL tested so far, but not in those from healthy adults. ATLV protein of MW 42,000 was at least one of the ATL-associated antigen(s) that were previously detected in ALT-leukemic cells by all sera from patients with ATL. These finding on the close association of ATLV protein and proviral DNA with ATL are direct evidence for the possible involvement of the retrovirus ATLV in leukemogenesis of human ATL.