George M. Shaw

The Family of Human T-Cell Leukemia Viruses and Their Role in the Cause of T-Cell Leukemia and AIDS

HTLV is the generic name we gave the first human retroviruses. The majority of isolates are very closely related; we call them human T-cell leukemia virus type I (HTLV-I). HTLV-I is endemic (at low rates) in the Caribbean, South and Central America, southeast U.S., southern Japan, and especially Africa. Viruses closely related to HTLV-I, but distinct from it, have been isolated from Old World monkeys. This and other facts led us to propose that the ancestral origin of HTLV is in Africa. Evidence indicates that HTLV-I is the direct cause of an aggressive form of adult T-cell leukemia and lymphoma. The mechanisms involved in the in vitro immortalization and in vivo malignancy are not yet clear but apparently do not involve any visible consistent chromosomal change, consistent virus expression, or known onc genes. Whichever the mechanism for growth induction by HTLV-I, its efficiency in causing malignancy may be because it has dual major effects on infected cells: (1) immortalization of some T cells, and (2) interference with function and cytopathic changes in many others. In collaboration with D. Golde and colleagues, we also discovered a second class of human T-lymphotropic retroviruses (HTLV-II). It shares many features with HTLV-I but has major genomic differences.

Etiology of AIDS: Biological and Biochemical Characteristics of HTLV-III

The newly identified human HTLV-III virus, the etiologic agent for AIDS, shares many of the biological and physicochemical properties common to a family of retroviruses named human T-cell leukemia (lymphotropic) viruses, or HTLV. Because of the similarities, and because of the uniform nomenclature for human T-cell leukemia (lymphotropic) viruses adopted at the first Cold Spring Harbor Meeting on HTLV (19, 79), this newly discovered virus associated with AIDS as HTLV-III was named HTLV-III. Other investigators making independent isolations of virus have suggested naming the virus lymphadenopathy virus or LAV (3, 16), immunodeficiency associated virus or IADV (48), AIDS-related virus (41). Immunological and nucleic acid comparison has now demonstrated that these viruses are, not surprisingly, very similar to HTLV-III (55, 63, 78). In view of the wide range of disease manifestations caused by the virus, and previous discussions concerning a uniform nomenclature for human T-lymphotropic retroviruses, it would seem ill-advised to restrict the name of this virus to one clinical manifestation of one disease. The frequent isolation of HTLV-III from patients with AIDS and ARC, the detection of antibodies specific for HTLV-III in nearly all patients with these diseases and in a high proportion of individuals at risk, and finally its effect on cells in vitro, leaves little doubt that HTLV-III is causatively involved in the development of these diseases. This etiologic association is further strengthened by the detection of HTLV-III infection in many instances where a direct cause-and-effect association can be made, e.g., hemophiliacs and children with AIDS, and blood from HTLV-III infected donors and the otherwise normal recipients of this blood who subsequently develop AIDS.