Characterization and distribution of nucleic acid sequences of a novel type C retrovirus isolated from neoplastic human T lymphocytes.

Abstract

A type C retrovirus (designated HTLV) recently isolated from a cell line derived from a lymph node and later from peripheral blood of a person with cutaneous T-cell lymphoma (mycosis fungoides) was characterized by nucleic acid hybridization experiments. HTLV Retroviruses have been isolated from many species (1, 2), and some are involved in the etiology of naturally occurring leukemias, lymphomas, and sarcomas of animals (1-3). Virus-related components have been detected in human tissues (for reviews, see refs. 2 and 3) but in the rare instances in which replicating virus has been isolated, such isolates have been closely related to previously described primate viruses, especially simian sarcoma virus (SSV), and the possibility of laboratory contamination could not be precluded. Recently, a type C virus was isolated from a human histiocytic lymphoma which, although again related to viruses of the SSV/gibbon ape leukemia virus (GALV) group, shows apparent differences (4).Detection of complete retrovirus particles is generally obtained only after in vitro cell proliferation (5), and in animal leukemias and lymphomas, T lymphocytes are often the target cells for virus infection (6). With rare exceptions, these cells could not be grown in vitro from human specimens, precluding the possibility of virus isolation. However, continuous in vitro growth of normal (7,8) and neoplastic (9) human T lymphocytes was recently made possible by the finding of a growth factor, termed "T-cell growth factor (TCGF)" (7, 8), which has now been purified (10). Normal T cells require prior activation by antigen or phytohemagglutinin to develop TCGF receptors, after which they respond to TCGF (10). In contrast, purified TCGF produces continuous growth of neoplastic T cells directly, without initial stimulation (9).We recently described the isolation of a type C virus, called "HTLV," from human neoplastic T lymphocytes cultured from blood and from a lymph node of a patient with cutaneous T-cell lymphoma (mycosis fungoides) (11). Electron microscopic examination and the presence of particulate media reverse transcriptase activity indicated that these cells were producing a type C virus. This reverse transcriptase activity was not inhibited by antisera to reverse transcriptases from a number of previously described retroviruses, including SSV [simian sarcomaassociated virus (SSAV)]/GALV and baboon endogenous type C virus (BaEV) (11).Here we describe an analysis of the nucleotide sequences of HTLV. The sequence homologies of [3H]cDNA and RNA of HTLV were compared to those of known animal retroviruses by molecular hybridization. In addition, the level of HTLV sequences (DNA and RNA) in the human T cells producing HTLV was assessed. Normal human DNA was tested for sequence homology with HTLV to determine whether HTLV is a germline-transmitted endogenous virus of humans or one that may be acquired after fertilization. MATERIALS AND METHODSCells and Viruses. The T cells of origin for HTLV (designated HUT 102 and originating from the ly...

Viral Aetiology of Adult T-Cell Leukaemia

“…In 1980 and 1981, human T-cell leukaemia virus (HTLV) and adult T-cell leukaemia (ATL) virus (ATLV) were isolated independently in the U.S.A. from an aggressive type of T-cell malignancy and in Japan from a patient with ATL, respectively (Poiesz et al, 1980Hinuma et aL, 1981 ;Yoshida et aL, 1982). Both viruses exhibited close similarities to the hitherto known animal retroviruses but were different structurally and immunologically (Rho et al, 1981 ;Reitz et al, 1981 ;Kalyanaraman et al, 1981). These two viruses quickly attracted the attention of a number of virologists and haematologists and the aetiological role of these viruses in mature T-cell malignancy was investigated extensively.…”

The Human T-Cell Leukemia Virus Family, Adult T Cell Leukemia, and AIDS

“…1) and, like other retroviruses, contains both a reverse transcriptase and high-molecularweight polyadenylated genomic RNA. HTLV-I was shown to be unique by the criteria of protein serology [14,37,38] and nucleic acid hybridization [35], and to be exogenous to man [35]. Transmission is horizontal and does not occur genetically [9,54].…”

“…The T cell lines were established from black patients in the United States with what were diagnosed as unusually aggressive variants of cutaneous T cell lymphoma [28,29,35]. The virus, which we called H1LV-I, has typical retrovirus morphology ( Fig.…”

Presence of HTLV in a Subset of T Cells from an Infected Patient: Some Immunochemical Properties of the Infected Cells

“…HTLV was shown to be unrelated to previously described retroviruses and not endogenous to humans, and integrated proviral DNA was present and expressed into mRNA in the malignant T cells of the Same patient [5]. A closely related virus was subsequently isolated from a patient with cutaneous T-cell leukemia-lymphoma [4].…”

“…The presence of HTLV was assayed in at least one of several ways: (1) p19 was assayed by indirect immunofluorescence using a murine monoclonal antibody; (2) p24 was assayed with a RIP assay using goat hyperimmune Sera (see Sarngadharan et al, this volume); (3) RNA and (4) DNA were assayed by liquid hybridization as described by Reitz et al [5].…”