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Heteroduplex Mapping in the Molecular Analysis of the Human T-Cell Leukemia (Lymphotropic) Viruses¹

Laboratory of Cell and Molecular Structure, Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland 21701 [M. A. G.]; Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland 20205 [F. W-S., R. C. G.]; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 20205 [J. E. C.]; and Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland 21701 [R. V. G.]

The human T-cell lymphotropic virus (HTLV) family includes members associated with T-cell cancers (HTLV-I and HTLV-II) as well as the etiological agent of the acquired immunodeficiency syndrome (HTLV-III). Molecular clones of these viruses were used in heteroduplex mapping experiments to study their structural and evolutionary relationships. The HTLV-I subgroup, despite some restriction enzyme site polymorphism, demonstrated a high degree of sequence conservation. Heteroduplexes of HTLV-I and HTLV-II demonstrated a significant amount of sequence homology, with the strongest region of conservation occurring in the 3'-most coding sequences, designated pX, and to a lesser, although substantial extent in the rest of the genome. Thus, the genomic organization of HTLV-II appears to be very similar to that of HTLV-I. All HTLV-III molecular clones appeared to be identical, with a single exception, which showed heterogeneity in the env gene region. In heteroduplexes between HTLV-I and HTLV-III, very little homology was observed, being confined to the gag/pol region. In contrast to the latter result, a striking amount of homology was detected between HTLV-III and a morphologically similar, pathogenic, nononcogenic lentivirus, visna virus. These data provide strong evidence for a close taxonomic and thus evolutionary relationship between HTLV-III and the lentivirus subfamily of retroviruses. A taxonomic tree, based on the genetic relatedness and biological properties of the HTLV family, is proposed.