Molecular characterization of human T-lymphotropic leukemia virus type III associated with the acquired immunodeficiency syndrome.

A T-lymphotropic retrovirus with cytopathic but not immortalizing activity has been isolated repeatedly from patients with acquired immune deficiency (AIDS) or lymphadenopathy syndrome (LAS) and successfully transmitted to a T-cell line (HT) for continuous production. Seroepidemiology data and the OKT4 tropism and cytopathogenicity of this virus indicate it is the etiological agent of AIDS. We have cloned HTLV-III genomes using three approaches: (1) cDNA clones were obtained from a cDNA plasmid library constructed from RNA of purified virions using oligo (dT) primers; (2) unintegrated provirus clones were obtained from Hirt supernatants of acutely infected H9 cells using virus from H9/HTLV-III; (3) clones of integrated provirus with flanking cellular sequences were obtained from a genomic DNA library of H9/HTLV-III. Analyses of these clones show that the HTLV-III genome is similar in size to those of HTLV-I and HTLV-II and contains a gene that functions as a transcriptional activator. Different isolates of HTLV-III display greater polymorphism than different isolates of HTLV-I among each other, possibly due to the highly replicative nature of HTLV-III. Viral sequences could be detected in fresh lymph node tissues of some AIDS patients, but even in the positive samples the number of infected cells is small (less than 1%). In both fresh tissues that are positive for viral sequences and HTLV-III infected cell lines, a substantial amount of unintegrated viral DNA is present in addition to integrated provirus. This is an unusual finding for retroviruses but may be significant in the cytopathicity of HTLV-III as has been proposed for some avain retroviruses.