The discovery of HTLV-1, the first pathogenic human retrovirus

Abstract

After the discovery of retroviral reverse transcriptase in 1970, there was a flurry of activity, sparked by the "War on Cancer," to identify human cancer retroviruses. After many false claims resulting from various artifacts, most scientists abandoned the search, but the Gallo laboratory carried on, developing both specific assays and new cell culture methods that enabled them to report, in the accompanying 1980 PNAS paper, identification and partial characterization of human T-cell leukemia virus (HTLV; now known as HTLV-1) produced by a T-cell line from a lymphoma patient. Follow-up studies, including collaboration with the group that first identified a cluster of adult T-cell leukemia (ATL) cases in Japan, provided conclusive evidence that HTLV was the cause of this disease. HTLV-1 is now known to infect at least 4-10 million people worldwide, about 5% of whom will develop ATL. Despite intensive research, knowledge of the viral etiology has not led to improvement in treatment or outcome of ATL. However, the technology for discovery of HTLV and acknowledgment of the existence of pathogenic human retroviruses laid the technical and intellectual foundation for the discovery of the cause of AIDS soon afterward. Without this advance, our ability to diagnose and treat HIV infection most likely would have been long delayed.

Keywords: adult T-cell leukemia; human retrovirus.

Fig. 1.

Thin section electron micrographs of HUT-102 cells. (A–D) “C-type” particles in various stages of budding and maturation. (E) IUdR-induced cell showing large numbers of budding and released particles, some of which are enlarged in the Inset. (Scale bars, A–D and Inset, 100 nm; E, 1,000 nm.) Reproduced with permission from ref. .

Fig. 2.

Properties of HTLV particles released by HUT-102 cells. (Left) RT activity of purified virions after equilibrium density gradient ultracentrifugation in a sucrose gradient. Incorporation of radiolabeled deoxynucleotide was monitored for each fraction with a variety of template primers: poly(C):oligo (dG) (x), poly(A):oligo (dT) (open circles), poly (dA):oligo (dT) (with Mn⁺⁺ instead of Mg⁺⁺; filled triangles). Filled circles show the density, in gm/mL. Banding of RT-containing particles at 1.16 g/mL is typical of retroviruses. (Right) Polyacrylamide gel electrophoresis of proteins from purified virions. Lanes 1 and 2, HTLV from HUT-102 cells; lane 3, simian sarcoma virus; lane 4, murine leukemia virus; lane 5, markers, whose molecular weight is shown to the right. Reproduced with permission from ref. .