Nakahara memorial lecture. Human T-cell leukemia virus type I: molecular biology and its implications in adult T-cell leukemia.

Isolation and characterization of the human T-cell leukemia virus (HTLV) type I was carried out from patients with adult T-cell leukemia (ATL). Total nucleotide sequence of the provirus genome was determined and the HTLV was distinguished from other retroviruses by a unique gene pX and also by its extremely long R sequence in the long terminal repeat (LTR). HTLV was demonstrated to be a causative agent of ATL by monoclonal integration of the proviruses in ATL cells. However, nonspecific provirus integration in ATL cells disproved the direct insertional activation of a specific cellular onc gene, eventually suggesting that a transacting viral function was involved in the leukemogenesis. A gene product of the unique gene pX and trans-activation of the transcription by the product was identified. This pX gene function might explain the leukemogenesis in ATL. The mass-production of the env gene products and their identified function provided information useful for developing the systems for diagnosis and prevention of HTLV infection and ATL.