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Human T-cell leukemia virus: its discovery and role in leukemogenesis and immunosuppression
Abstract:
We have highlighted the events leading to the discovery of the first human RNA tumor virus and then reviewed what is currently known about its biology. From this, it is clear that we have only begun to appreciate the biologic diversity, the geographic distribution, and the disease spectrum of this family of human T-lymphotropic retroviruses which we collectively term HTLV. At a basic level, HTLV provides a unique opportunity to study in vitro and in vivo mechanisms of cell transformation. Given its close association with adult T-cell leukemia and its ability to efficiently immortalize primary cells in vitro, we believe that HTLV will very likely harbor clues to the biology of cell growth, differentiation, and transformation. At a more clinical level, the close association between HTLV and a malignancy of clonally expanded (HTLV-containing) mature T-cells argues strongly for a causal relationship, although the mechanism for such is currently unknown. It is likely that further study of the molecular and cellular biology of this virus will bring together these basic and clinical findings and elucidate, at least in part, one mechanism for human leukemogenesis. From a more speculative viewpoint, the role of HTLV in the pathogenesis of human disease appears even broader. As discussed in this chapter, there are indications that all subtypes of HTLV may produce immunosuppression both in vitro and in vivo, and there is now exciting new data to suggest that a novel member of this family of viruses, HTLV-III, is causally linked to the AIDS syndrome. Moreover, the possibility has been raised that the immunosuppressive properties of HTLV could predispose patients to non-T-cell malignancies as occurs in patients with AIDS or chemically induced immunosuppression. Finally, by employing the experimental strategies which were successful in isolating HTLV-I, HTLV-II, and HTLV-III, it may be possible in the future to identify still other human retroviruses.